Stem Cell and Exosome Therapies in Mesial Temporal Sclerosis: A Case Report

Stem Cell and Exosome Therapies in Mesial Temporal Sclerosis: A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Stem Cell and Exosome Therapies in Mesial Temporal Sclerosis: A Case Report Eduardo Ciarrochi, Juan Bautista Ciarrochi, Ugartemendía Leonardo Adrián This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8309899/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Mesial temporal sclerosis (MTS) is a well-defined form of structural focal epilepsy, characterised by neuronal loss and gliosis in the hippocampus and surrounding structures. It is associated with a neurotoxic microenvironment that disrupts neurogenesis, synaptogenesis and dendritic spine plasticity, leading to cognitive, memory, and emotional impairments. The aim of presenting this case is to show the clinical and imaging progress after starting treatment with stem cells and exosomes for this condition. Case report: We present the case of a 15-year-old patient, clinically and radiologically diagnosed with MTS, who exhibited severe cognitive, emotional, and behavioural impairments, including working memory deficits, receptive and expressive language disturbances and significant attention deficits. Conclusions: Stem cells exhibit immunomodulatory properties, promoting an anti-inflammatory profile and facilitating tissue regeneration at injury sites . This case report highlights the therapeutic potential of the combination therapy with autologous stem cells and exosomes as a novel approach to regenerating structural and functional impairments in MTS. Exosomes Hippocampal Sclerosis Hippocampus Immunomodulation Stem cells Figures Figure 1 Figure 2 Figure 3 Background Mesial temporal sclerosis (MTS) is a well-defined entity of structural focal epilepsy characterised by gliosis and neuronal loss in the hippocampus and surrounding structures [ 1 ]. This neuronal loss is particularly significant in the dentate gyrus and in the CA1 (Sommer's area) and CA3 regions of the hippocampus, with a preference for pyramidal cells [ 2 ]. Immune dysregulation has been observed in epileptic patients, with increased levels of cytokines, such as IL-1B, IL-18, CCL2, CCL3, and CCL4, indicating that inflammation is an important component of epileptogenesis [ 2 ]. Their seizures are distinguished by their complexity and clinical heterogeneity, involving sensory, psychic, mnestic and motor signs and symptoms. This condition is associated with a state of neurotoxicity causing early neuronal death, destruction of glial cells, and oxidative stress [ 3 ]. Likewise, astrocytic function is impaired, thus affecting neuronal development, synaptogenesis, and neurogenesis [ 4 ]. All of this is accompanied by an impaired expression of glucocorticoid receptors and the concentrations of this hormone in the hippocampus, causing atrophy and decreased dendritic spine density [ 5 ]. This contributes to the loss of plasticity of these structures, which is associated with the memory deficits typical of the condition. The hippocampus is a strong regulator of the hypothalamic-pituitary-adrenal axis. This feature is diminished due to the hippocampal structural and functional impairment present in MTS. The aim of this study is to present a case of mesial temporal sclerosis and its clinical and imaging development after starting treatment with stem cells and exosomes. Clinical case A 15-year-old patient presenting with focal epilepsy clinically and radiologically characterised as MTS. Normal neurodevelopment in the acquisition of gross and fine motor skills, walking, language and bladder and bowel control. Throughout her childhood, she experienced events of febrile seizures and was diagnosed with epilepsy in 2022. The patient presents various pre-critical (prodromes and aura), critical, post-critical, and intercritical manifestations. At the age of five, difficulties in balance and fine motor skills were noticed. Clinically, the patient presents with severe momentary attention deficits, staring at a single point and losing contact with her surroundings. She exhibits significant complications in her visuospatial cognitive ability and working memory. She experiences disorders in both receptive and expressive language. Regarding the former, she has difficulty in performing tasks related to verbal imitation or dictation in writing, as well as in reading and comprehension. In line with this, instructions or questions must be repeated to her as she remains silent without responding, showing a clear disconnection from her surroundings. Regarding the second aspect of language, her speech is sometimes incomprehensible, she speaks softly and finds it difficult to maintain an appropriate conversation. In October 2024, she was admitted to a psychiatric hospital due to a severe depressive event with psychotic symptoms. The magnetic resonance scan prior to the proposed therapy showed the following characteristics: “bilateral dilation of the temporal horns, accompanied by a decrease in the volume of the hippocampi, predominantly on the right side” (Fig. 1). Comments Stem cells are undifferentiated cells with the capacity for self-renewal and differentiation into various types of tissue. They interact closely with the immune system and can act on the inflammatory microenvironment present in various conditions [ 6 ]. In turn, they secrete a wide range of active biomolecules such as proteins, nucleic acids, exosomes, and microvesicles, which are collectively released through structures known as secretomes [ 7 ]. This complex complements the regenerative and therapeutic capacity of stem cells [ 7 ]. Through cellular mechanisms (action on Treg lymphocytes, macrophages) and humoral mechanisms (exosomes, secretomes), stem cells exert an immunomodulatory action capable of regulating inflammation and promoting tissue repair. This property makes them a therapeutic strategy for different types of diseases [ 6 ]. We highlight the recent interest that has emerged in the superficial fascia as an important niche and reservoir for stem cells [ 8 ]. It stands out as a biologically active environment capable of regulating stem cell survival, modulating the immune system, and with a strong regenerative potential [ 8 ]. This tissue constitutes a biologically active platform and a communication pathway for the transport and circulation of stem cells, thus being a strong enhancer of angiogenesis and cell survival. This positions the superficial fascia as a dynamic, multifunctional, and biologically active tissue [ 9 ]. Its structure contains a high density of fibroblasts, which secrete multiple bioactive factors, especially the fibroblast growth factor (FGF) family [ 10 ]. These factors interact with an enzyme called telomerase, over which they induce the expression of its TERT (telomerase reverse transcriptase) subunit, promoting the survival and differentiation of neuronal precursors, adult stem cells, and nerve cells [ 11 ]. In these cells, it modulates excitotoxicity [ 11 ], a pathological mechanism that perpetuates extensive damage to nerve tissue. Telomerase plays a critical role in cell proliferation and differentiation, neuronal survival, and neurogenesis. Its TERT subunit is widely expressed in strategic locations in the adult brain, such as the hippocampus [ 11 ]. It is because of this function in neuronal development that telomerase may be involved in conditions such as anxiety, depression, or memory problems [ 11 ], all of which were observed in the patient. Another important point in our proposed strategy is cell-free therapy, based on the application of exosomes. These have an important therapeutic function, acting as vehicles for molecules that are supported by structures called “lipid rafts”, which facilitate neurogenesis and neuronal migration [ 12 ]. These premises at the cellular, enzymatic, immunological, and functional level help to further understand the clinical and structural advances observed in this case of MTS. These will be chronologically presented below. During the first encounter with the patient, she was admitted with minimal communicative intent, establishing contact only with her sister, who responded on her behalf. During the stem cell extraction procedure, she experienced an event of neurovegetative dysregulation characterised by excessive sweating, skin flushing and vasotonic abnormalities consistent with a neurovegetative reaction. The procedure went on successfully. In subsequent check-ups, which were accompanied by the application of autologous stem cells and exosomes, a progressive improvement in higher cognitive abilities was observed, particularly in attention, memory, and language. The patient progressively reduced events of interrupted thinking and staring at a single point, increasing her attention to her surroundings as well as her ability to understand and perform the tasks she was asked for, both physical and mental. Correlation with hippocampal regeneration is reflected in the recovery of anterograde memory, enabling her to successfully perform tasks and retain short-term information, facilitating, for example, the performance of exercise routines and fine coordination activities. In turn, her retrograde memory was improved, enabling her to recall memories and recount experiences during subsequent visits, something that was previously unthinkable. The patient began to express personal interests, engage in consistent dialogues appropriate for her age, and her language was enriched with a greater variety of words and detailed descriptions. Overall, progressive cognitive, emotional, and social maturity is observed, exhibiting a significantly more adapted and functional developmental profile. All these advances are consistent with findings in the MRI scan of June 27, 2025, which marks the beginning of regeneration in the hippocampal region. Such image was reported to be normal (Fig. 2 and Fig. 3 ). Conclusions MTS is a complex entity characterised by structural impairments accompanied by heterogeneous clinical signs .This is arranged in a microenvironment of neurotoxicity, where essential functions of nervous tissue, such as neurogenesis, synaptogenesis and plasticity, are affected. Stem cells have immunomodulatory properties and can promote an anti-inflammatory profile at both the cellular and humoral level, favouring regeneration of the affected tissue. On the other hand, elements other than stem cells, such as fibroblasts, FGF, telomerase, exosomes and secretomes, play a vital role in cell proliferation, neuronal development and neurogenesis. The patient showed significant progress in various areas of her neurological development, such as attention, memory, language and social interaction. Together, these provide her with a more adapted and functional developmental profile appropriate for her age. Combination therapy with stem cells and exosomes represents a novel treatment for mesial temporal sclerosis. Clinical and imaging advances observed in this case position it as a promising therapy for this complex disease. Abbreviations MTS Mesial temporal sclerosis Declarations The content of the manuscript has not been published, or submitted for publication elsewhere Ethics approval and consent to participate: Not applicable Consent for publication: Consent for publication of the case report was obtained from the patient family Availability of data and materials: Not applicable Competing interests: the authors declare that they have no competing interests Funding: No funding Authors' contributions: E.C conceived the article. J.B.C collected and interpreted the patient’s clinical data. E.C and J.B.C wrote and edited the manuscript. L.A.U reviewed and edited the manuscript. All authors have read and approved the final version of the manuscript. Acknowledgements: not applicable References Monge-Galindo L, Pérez-Delgado R, López-Pisón J, Lafuente-Hidalgo M, del Ruiz I, Peña-Segura JL (2010) Esclerosis mesial temporal en pediatría: espectro clínico. Nuestra experiencia de 19 años. Rev Neurol 50:341–348 Villamizar-Torres D, Cepeda Trillos AC, Vargas-Moreno A (2024) Mesial temporal sclerosis and epilepsy: a narrative review. Acta Epileptol 6:28 Mendel Nzogang P, Boris Donkeng M, Neuroprotection (2020) The Way of Anti-Inflammatory Agents. Neuroprotection - New Approaches and Prospects. IntechOpen Çarçak N, Onat F, Sitnikova E (2023) Astrocytes as a target for therapeutic strategies in epilepsy: current insights. Front Mol Neurosci 16:1183775 Liston C, Gan W (2011) Glucocorticoids are critical regulators of dendritic spine development and plasticity in vivo. Proc Natl Acad Sci USA 108(38):16074–16079 Shi Y, Wang Y, Li Q, Liu K, Hou J, Shao C et al (2018) Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases. Nat Rev Nephrol 14:1–15 Karimian A, Khoshnazar SM, Kazemi T et al (2024) Role of secretomes in cell-free therapeutic strategies in regenerative medicine. Cell Tissue Bank 25:411–426 Pirri C, Pirri N, Petrelli L, De Caro R, Stecco C (2025) Redefining Fascia: A mechanobiological hub and stem cell reservoir in regeneration—a systematic review. Int J Mol Sci 26:10166 Ciarrochi E, Re (1992) Structure and Construction: The System of Skin Flaps. Ann Plast Surg 29(5):476 Yun YR, Won JE, Jeon E, Lee S, Kang W, Jo H et al (2010) Fibroblast growth factors: biology, function, and application for tissue regeneration. J Tissue Eng 2010:218142 Liu MY, Nemes A, Zhou QG (2018) The emerging roles for telomerase in the central nervous system. Front Mol Neurosci 11:160 Viljetić B, Blažetić S, Labak I, Ivić V, Zjalić M, Heffer M, Balog M (2024) Lipid Rafts: The Maestros of Normal Brain Development. Biomolecules 14(3):362 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8309899","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":560493871,"identity":"e22af897-a4c7-4cc4-8788-26efea3a94f4","order_by":0,"name":"Eduardo Ciarrochi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/0lEQVRIiWNgGAWjYDCCAxCKB0wyNkjIGYBZBhb4tDA2IGsxNmBgBmmRIKiFAaqFIXEDWAsDbi18x5ufP/i4x06Gf/bZhw9+7rBI387ef3TDjwIJBv727gRsWiTPHDNsnPEsmUfiXLqxYe8ZidydPYfZbvYAHSZx5uwGbFoMbuQwNvMcOMDDcIaNTZqxTSJ3w41kths8QC0GQDZeLfJQLekGQC03/xCjxQCqJQGk5TY+W0B+mTnjQDKP4Rk2ZsPeNgnDDWcOm92WMZDgweUXYIg9+PDhgJ293Bk2xgc/2+rkDY43Prv55o+NHH97L1YtuAEPacpHwSgYBaNgFCADAJWOYfGAvmFUAAAAAElFTkSuQmCC","orcid":"","institution":"","correspondingAuthor":true,"prefix":"","firstName":"Eduardo","middleName":"","lastName":"Ciarrochi","suffix":""},{"id":560493872,"identity":"147c52f9-90a9-4d31-a5d6-440d44e2a135","order_by":1,"name":"Juan Bautista Ciarrochi","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Juan","middleName":"Bautista","lastName":"Ciarrochi","suffix":""},{"id":560493873,"identity":"5c4b6f5f-586f-4350-81b0-6aff8578277a","order_by":2,"name":"Ugartemendía Leonardo Adrián","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Ugartemendía","middleName":"Leonardo","lastName":"Adrián","suffix":""}],"badges":[],"createdAt":"2025-12-08 16:53:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8309899/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8309899/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":98293827,"identity":"ad86a6b8-4cea-45b9-a1fd-439d994d6aec","added_by":"auto","created_at":"2025-12-16 09:03:50","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":124951,"visible":true,"origin":"","legend":"","description":"","filename":"Originalmanuscript.docx","url":"https://assets-eu.researchsquare.com/files/rs-8309899/v1/deccc3537644260c13f71c72.docx"},{"id":98435341,"identity":"58dab4a6-2d4a-4a59-b06a-d70a5cbf9484","added_by":"auto","created_at":"2025-12-17 16:53:30","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":4637,"visible":true,"origin":"","legend":"","description":"","filename":"767fdb0779004163814d994ce0315412.json","url":"https://assets-eu.researchsquare.com/files/rs-8309899/v1/84127212faf63631ffb6a8b1.json"},{"id":98293825,"identity":"8c47cafd-4f43-41ef-a0e1-cd478559be13","added_by":"auto","created_at":"2025-12-16 09:03:50","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":34296,"visible":true,"origin":"","legend":"","description":"","filename":"767fdb0779004163814d994ce03154121enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-8309899/v1/9d9c26d40faa89f47d9c98a9.xml"},{"id":98434252,"identity":"96852b7c-7a16-4eb4-a540-577418aba86c","added_by":"auto","created_at":"2025-12-17 16:51:47","extension":"jpeg","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":21750,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8309899/v1/f7bbf4b2fcb435679a28c122.jpeg"},{"id":98293833,"identity":"253245b9-57cd-45b3-b324-805c2419e691","added_by":"auto","created_at":"2025-12-16 09:03:50","extension":"jpeg","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":32470,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8309899/v1/1f1aa0e1443057a6f0a55fc0.jpeg"},{"id":98293828,"identity":"b6ab41c8-27d4-44e9-88f7-5245d2427db9","added_by":"auto","created_at":"2025-12-16 09:03:50","extension":"jpeg","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":48184,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8309899/v1/258074745ea9c9aee3dec7d9.jpeg"},{"id":98435104,"identity":"04fa4212-8db1-4ce3-88e2-5b09c9c5a86d","added_by":"auto","created_at":"2025-12-17 16:53:07","extension":"png","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":122407,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8309899/v1/35ef13f7f6c9e844bd6428da.png"},{"id":98436251,"identity":"08c1b2d6-67e2-48dd-bdb0-351f32ba9682","added_by":"auto","created_at":"2025-12-17 16:55:13","extension":"png","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":35816,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8309899/v1/c01628e8182b2c99f47c1349.png"},{"id":98293836,"identity":"7529eb7f-d0b1-4c19-ba67-46e6c9e099ef","added_by":"auto","created_at":"2025-12-16 09:03:51","extension":"png","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":359757,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8309899/v1/f1ad45f113595d0dd390ab97.png"},{"id":98293834,"identity":"5581b144-f85c-4234-9a59-c67a41ec5122","added_by":"auto","created_at":"2025-12-16 09:03:50","extension":"xml","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":33097,"visible":true,"origin":"","legend":"","description":"","filename":"767fdb0779004163814d994ce03154121structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8309899/v1/9e1326251ae16a0a0e234e47.xml"},{"id":98293835,"identity":"ff021b99-f772-4f11-8025-e882a901208e","added_by":"auto","created_at":"2025-12-16 09:03:50","extension":"html","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":38807,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8309899/v1/9d25acd0696bf49b63f2f320.html"},{"id":98293823,"identity":"e7537f34-fca1-48a4-b4af-d7f7a4e54d0c","added_by":"auto","created_at":"2025-12-16 09:03:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":227584,"visible":true,"origin":"","legend":"\u003cp\u003eCoronal FLAIR sequence. Decrease in the volume of the hippocampi, predominantly on the right side.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8309899/v1/ab377f7bb348674fcf4f1154.png"},{"id":98435025,"identity":"0370bc6c-fd04-4756-83ac-76b68c6f5ba5","added_by":"auto","created_at":"2025-12-17 16:52:57","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":354438,"visible":true,"origin":"","legend":"\u003cp\u003eCoronal T2 sequence. Hippocampal region with preserved signal, volume and morphology.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8309899/v1/24e7e14d4da39a088064fcfe.png"},{"id":98435539,"identity":"f3bdb22b-f794-4ba1-92e4-27622494a477","added_by":"auto","created_at":"2025-12-17 16:54:02","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":280927,"visible":true,"origin":"","legend":"\u003cp\u003eAxial T2 sequence. Hippocampi with preserved morphology and non-dilated temporal horns.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8309899/v1/a4a8ae8169ccfcc976b2c251.png"},{"id":98622993,"identity":"637711ae-48fd-4e06-bf41-a50b37412608","added_by":"auto","created_at":"2025-12-19 17:03:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1391066,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8309899/v1/a9d06b27-8995-4e43-aafc-2c0830d3fe1f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Stem Cell and Exosome Therapies in Mesial Temporal Sclerosis: A Case Report","fulltext":[{"header":"Background","content":"\u003cp\u003eMesial temporal sclerosis (MTS) is a well-defined entity of structural focal epilepsy characterised by gliosis and neuronal loss in the hippocampus and surrounding structures [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This neuronal loss is particularly significant in the dentate gyrus and in the CA1 (Sommer's area) and CA3 regions of the hippocampus, with a preference for pyramidal cells [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Immune dysregulation has been observed in epileptic patients, with increased levels of cytokines, such as IL-1B, IL-18, CCL2, CCL3, and CCL4, indicating that inflammation is an important component of epileptogenesis [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Their seizures are distinguished by their complexity and clinical heterogeneity, involving sensory, psychic, mnestic and motor signs and symptoms.\u003c/p\u003e \u003cp\u003eThis condition is associated with a state of neurotoxicity causing early neuronal death, destruction of glial cells, and oxidative stress [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Likewise, astrocytic function is impaired, thus affecting neuronal development, synaptogenesis, and neurogenesis [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. All of this is accompanied by an impaired expression of glucocorticoid receptors and the concentrations of this hormone in the hippocampus, causing atrophy and decreased dendritic spine density [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. This contributes to the loss of plasticity of these structures, which is associated with the memory deficits typical of the condition. The hippocampus is a strong regulator of the hypothalamic-pituitary-adrenal axis. This feature is diminished due to the hippocampal structural and functional impairment present in MTS. The aim of this study is to present a case of mesial temporal sclerosis and its clinical and imaging development after starting treatment with stem cells and exosomes.\u003c/p\u003e"},{"header":"Clinical case","content":"\u003cp\u003eA 15-year-old patient presenting with focal epilepsy clinically and radiologically characterised as MTS. Normal neurodevelopment in the acquisition of gross and fine motor skills, walking, language and bladder and bowel control. Throughout her childhood, she experienced events of febrile seizures and was diagnosed with epilepsy in 2022. The patient presents various pre-critical (prodromes and aura), critical, post-critical, and intercritical manifestations. At the age of five, difficulties in balance and fine motor skills were noticed.\u003c/p\u003e \u003cp\u003eClinically, the patient presents with severe momentary attention deficits, staring at a single point and losing contact with her surroundings. She exhibits significant complications in her visuospatial cognitive ability and working memory. She experiences disorders in both receptive and expressive language. Regarding the former, she has difficulty in performing tasks related to verbal imitation or dictation in writing, as well as in reading and comprehension. In line with this, instructions or questions must be repeated to her as she remains silent without responding, showing a clear disconnection from her surroundings. Regarding the second aspect of language, her speech is sometimes incomprehensible, she speaks softly and finds it difficult to maintain an appropriate conversation. In October 2024, she was admitted to a psychiatric hospital due to a severe depressive event with psychotic symptoms. The magnetic resonance scan prior to the proposed therapy showed the following characteristics: \u0026ldquo;bilateral dilation of the temporal horns, accompanied by a decrease in the volume of the hippocampi, predominantly on the right side\u0026rdquo; (Fig.\u0026nbsp;1).\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eComments\u003c/h2\u003e \u003cp\u003eStem cells are undifferentiated cells with the capacity for self-renewal and differentiation into various types of tissue. They interact closely with the immune system and can act on the inflammatory microenvironment present in various conditions [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In turn, they secrete a wide range of active biomolecules such as proteins, nucleic acids, exosomes, and microvesicles, which are collectively released through structures known as secretomes [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. This complex complements the regenerative and therapeutic capacity of stem cells [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Through cellular mechanisms (action on Treg lymphocytes, macrophages) and humoral mechanisms (exosomes, secretomes), stem cells exert an immunomodulatory action capable of regulating inflammation and promoting tissue repair. This property makes them a therapeutic strategy for different types of diseases [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe highlight the recent interest that has emerged in the superficial fascia as an important niche and reservoir for stem cells [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. It stands out as a biologically active environment capable of regulating stem cell survival, modulating the immune system, and with a strong regenerative potential [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. This tissue constitutes a biologically active platform and a communication pathway for the transport and circulation of stem cells, thus being a strong enhancer of angiogenesis and cell survival. This positions the superficial fascia as a dynamic, multifunctional, and biologically active tissue [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Its structure contains a high density of fibroblasts, which secrete multiple bioactive factors, especially the fibroblast growth factor (FGF) family [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. These factors interact with an enzyme called telomerase, over which they induce the expression of its TERT (telomerase reverse transcriptase) subunit, promoting the survival and differentiation of neuronal precursors, adult stem cells, and nerve cells [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In these cells, it modulates excitotoxicity [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], a pathological mechanism that perpetuates extensive damage to nerve tissue.\u003c/p\u003e \u003cp\u003eTelomerase plays a critical role in cell proliferation and differentiation, neuronal survival, and neurogenesis. Its TERT subunit is widely expressed in strategic locations in the adult brain, such as the hippocampus [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. It is because of this function in neuronal development that telomerase may be involved in conditions such as anxiety, depression, or memory problems [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], all of which were observed in the patient.\u003c/p\u003e \u003cp\u003eAnother important point in our proposed strategy is cell-free therapy, based on the application of exosomes. These have an important therapeutic function, acting as vehicles for molecules that are supported by structures called \u0026ldquo;lipid rafts\u0026rdquo;, which facilitate neurogenesis and neuronal migration [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThese premises at the cellular, enzymatic, immunological, and functional level help to further understand the clinical and structural advances observed in this case of MTS. These will be chronologically presented below.\u003c/p\u003e \u003cp\u003eDuring the first encounter with the patient, she was admitted with minimal communicative intent, establishing contact only with her sister, who responded on her behalf. During the stem cell extraction procedure, she experienced an event of neurovegetative dysregulation characterised by excessive sweating, skin flushing and vasotonic abnormalities consistent with a neurovegetative reaction. The procedure went on successfully.\u003c/p\u003e \u003cp\u003eIn subsequent check-ups, which were accompanied by the application of autologous stem cells and exosomes, a progressive improvement in higher cognitive abilities was observed, particularly in attention, memory, and language. The patient progressively reduced events of interrupted thinking and staring at a single point, increasing her attention to her surroundings as well as her ability to understand and perform the tasks she was asked for, both physical and mental. Correlation with hippocampal regeneration is reflected in the recovery of anterograde memory, enabling her to successfully perform tasks and retain short-term information, facilitating, for example, the performance of exercise routines and fine coordination activities. In turn, her retrograde memory was improved, enabling her to recall memories and recount experiences during subsequent visits, something that was previously unthinkable. The patient began to express personal interests, engage in consistent dialogues appropriate for her age, and her language was enriched with a greater variety of words and detailed descriptions.\u003c/p\u003e \u003cp\u003eOverall, progressive cognitive, emotional, and social maturity is observed, exhibiting a significantly more adapted and functional developmental profile. All these advances are consistent with findings in the MRI scan of June 27, 2025, which marks the beginning of regeneration in the hippocampal region. Such image was reported to be normal (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eMTS is a complex entity characterised by structural impairments accompanied by heterogeneous clinical signs .This is arranged in a microenvironment of neurotoxicity, where essential functions of nervous tissue, such as neurogenesis, synaptogenesis and plasticity, are affected.\u003c/p\u003e \u003cp\u003eStem cells have immunomodulatory properties and can promote an anti-inflammatory profile at both the cellular and humoral level, favouring regeneration of the affected tissue. On the other hand, elements other than stem cells, such as fibroblasts, FGF, telomerase, exosomes and secretomes, play a vital role in cell proliferation, neuronal development and neurogenesis.\u003c/p\u003e \u003cp\u003eThe patient showed significant progress in various areas of her neurological development, such as attention, memory, language and social interaction. Together, these provide her with a more adapted and functional developmental profile appropriate for her age.\u003c/p\u003e \u003cp\u003eCombination therapy with stem cells and exosomes represents a novel treatment for mesial temporal sclerosis. Clinical and imaging advances observed in this case position it as a promising therapy for this complex disease.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eMTS Mesial temporal sclerosis\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThe content of the manuscript has not been published, or submitted for publication elsewhere\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate: Not applicable\u003c/p\u003e\n\u003cp\u003eConsent for publication: Consent for publication of the case report was obtained from the patient family\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials: Not applicable\u003c/p\u003e\n\u003cp\u003eCompeting interests: \u0026nbsp;the authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003eFunding: No funding\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; contributions: \u0026nbsp;E.C conceived the article. J.B.C collected and interpreted the patient\u0026rsquo;s clinical data. E.C and J.B.C wrote and edited the manuscript. L.A.U reviewed and edited the manuscript. All authors have read and approved the final version of the manuscript. \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAcknowledgements: \u0026nbsp;not applicable\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMonge-Galindo L, P\u0026eacute;rez-Delgado R, L\u0026oacute;pez-Pis\u0026oacute;n J, Lafuente-Hidalgo M, del Ruiz I, Pe\u0026ntilde;a-Segura JL (2010) Esclerosis mesial temporal en pediatr\u0026iacute;a: espectro cl\u0026iacute;nico. Nuestra experiencia de 19 a\u0026ntilde;os. Rev Neurol 50:341\u0026ndash;348\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVillamizar-Torres D, Cepeda Trillos AC, Vargas-Moreno A (2024) Mesial temporal sclerosis and epilepsy: a narrative review. Acta Epileptol 6:28\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMendel Nzogang P, Boris Donkeng M, Neuroprotection (2020) The Way of Anti-Inflammatory Agents. Neuroprotection - New Approaches and Prospects. IntechOpen\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003e\u0026Ccedil;ar\u0026ccedil;ak N, Onat F, Sitnikova E (2023) Astrocytes as a target for therapeutic strategies in epilepsy: current insights. Front Mol Neurosci 16:1183775\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eListon C, Gan W (2011) Glucocorticoids are critical regulators of dendritic spine development and plasticity in vivo. Proc Natl Acad Sci USA 108(38):16074\u0026ndash;16079\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShi Y, Wang Y, Li Q, Liu K, Hou J, Shao C et al (2018) Immunoregulatory mechanisms of mesenchymal stem and stromal cells in inflammatory diseases. Nat Rev Nephrol 14:1\u0026ndash;15\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKarimian A, Khoshnazar SM, Kazemi T et al (2024) Role of secretomes in cell-free therapeutic strategies in regenerative medicine. Cell Tissue Bank 25:411\u0026ndash;426\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePirri C, Pirri N, Petrelli L, De Caro R, Stecco C (2025) Redefining Fascia: A mechanobiological hub and stem cell reservoir in regeneration\u0026mdash;a systematic review. Int J Mol Sci 26:10166\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCiarrochi E, Re (1992) Structure and Construction: The System of Skin Flaps. Ann Plast Surg 29(5):476\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYun YR, Won JE, Jeon E, Lee S, Kang W, Jo H et al (2010) Fibroblast growth factors: biology, function, and application for tissue regeneration. J Tissue Eng 2010:218142\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu MY, Nemes A, Zhou QG (2018) The emerging roles for telomerase in the central nervous system. Front Mol Neurosci 11:160\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eViljetić B, Blažetić S, Labak I, Ivić V, Zjalić M, Heffer M, Balog M (2024) Lipid Rafts: The Maestros of Normal Brain Development. Biomolecules 14(3):362\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Exosomes, Hippocampal Sclerosis, Hippocampus, Immunomodulation, Stem cells","lastPublishedDoi":"10.21203/rs.3.rs-8309899/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8309899/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Mesial temporal sclerosis (MTS) is a well-defined form of structural focal epilepsy, characterised by neuronal loss and gliosis in the hippocampus and surrounding structures. It is associated with a neurotoxic microenvironment that disrupts neurogenesis, synaptogenesis and dendritic spine plasticity, leading to cognitive, memory, and emotional impairments. \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eThe aim of presenting this case is to show the clinical and imaging progress after starting treatment with stem cells and exosomes for this condition. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase report: \u003c/strong\u003eWe present the case of a 15-year-old patient, clinically and radiologically diagnosed with MTS, who exhibited severe cognitive, emotional, and behavioural impairments, including working memory deficits, receptive and expressive language disturbances and significant attention deficits.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eStem cells exhibit immunomodulatory properties, promoting an anti-inflammatory profile and facilitating tissue regeneration at injury sites\u003cstrong\u003e. \u003c/strong\u003eThis case report highlights the therapeutic potential of the combination therapy with autologous stem cells and exosomes as a novel approach to regenerating structural and functional impairments in MTS.\u003c/p\u003e","manuscriptTitle":"Stem Cell and Exosome Therapies in Mesial Temporal Sclerosis: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-16 09:03:45","doi":"10.21203/rs.3.rs-8309899/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"74e32f8c-07ee-4517-8252-4c40ce69a7ba","owner":[],"postedDate":"December 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-16T09:03:48+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-16 09:03:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8309899","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8309899","identity":"rs-8309899","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}