A novel therapeutic approach for endometriosis using adipose-derived stem cell-derived conditioned medium- A new hope for endometriotic patients in improving fertility

S Joseph Huang, Chun-Yen Huang, Chun‐Yen Huang, Yuhao Huang, Yu-Hao Huang, Jai-Hong Cheng, Jai‐Hong Cheng, Ya-Chun Yu, Jui-Chi Lai, Yi‐Pei Hung, Yi-Pei Hung, Chi-Chang Chang, Chi‐Chang Chang, Li‐Yen Shiu, Li-Yen Shiu
Frontiers in endocrinology · 2023 · vol. 14 , pp. 1158527 · doi:10.3389/fendo.2023.1158527 · PMID:37293500 · W4378072333
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

Adipose-derived stem cell-conditioned medium inhibited endometriosis growth and improved pregnancy outcomes in mice by reducing inflammation and angiogenesis.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 ⓘ

This paper examined whether adipose-derived stem cell-derived conditioned medium (ADSC-CM) could inhibit endometriosis development in an autologous endometriosis mouse model, comparing ADSC-CM, ADSCs, and ADSC-CM combined with ADSCs over 28 days. Human ADSCs and ADSC-CM underwent sterility, endotoxin, mycoplasma, growth promotion, and karyotyping quality checks under GMP/GTP, and the study assessed endometriotic cyst area, pelvic adhesions, inflammatory/angiogenic markers (ICAM-1 and VEGF), apoptosis (caspase 3), and pregnancy outcomes after mating. ADSC-CM reduced endometriotic cyst area and resorption rate and increased live birth/dam number and 1-week pup survival, while inhibiting ICAM-1 and VEGF expression; however, adding ADSCs alongside ADSC-CM blocked some of these inhibitory effects, and ADSCs increased adhesion by themselves. The paper’s mechanistic analysis highlighted PTX3 as a potentially critical mediator, and its caveat is that increased adhesions occurred with ADSC presence, complicating interpretation of efficacy. This paper is centrally about endometriosis — it tests ADSC-CM as an anti-endometriotic therapy and reports improved fertility-related outcomes in an endometriosis mouse model.

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Abstract

Introduction: Endometriosis is defined as the growth of endometrial glands and stromal cells in a heterotopic location with immune dysregulation. It usually leads to chronic pelvic pain and subfertility. Although various treatments are available, the recurrence rate remains high. Adipose tissue is an abundant source of multipotent mesenchymal adipose-derived stem cells (ADSCs). ADSCs display effects on not only tissue regeneration, but also immune regulation. Thus, the current study aims to test the effects of ADSCs on the growth of endometriosis. Methods: ADSCs isolated from lipoaspiration-generated adipose tissue and their conditioned medium (ADSC-CM) were subjected to quality validation, including karyotyping as well as growth promotion and sterility tests for microbial contamination under Good Tissue Practice and Good Manufacturing Practice regulations. An autologous endometriosis mouse model was established by suturing endometrial tissue to peritoneal wall followed by treating with DMEM/F12 medium, ADSC-CM, ADSCs or ADSC-CM+ADSCs for 28 days. The area of endometriotic cysts and the degree of pelvic adhesion were measured. ICAM-1, VEGF and caspase 3 expression was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. Moreover, the mice were allowed to mate and deliver. The pregnancy outcomes were recorded. The ADSC-CM was subjected to proteomics analysis with further data mining with Ingenuity Pathway Analysis (IPA). Results: Both ADSC-CM and ADSCs passed quality validation. ADSC-CM reduced the area of endometriotic cysts. The inhibition by ADSC-CM was obliterated by adding ADSCs. The presence of ADSCs with or without ADSC-CM increased the peritoneal adhesion. ADSC-CM inhibited ICAM-1 and VEGF mRNA and protein expression, whereas the addition of ADSCs not only did not inhibit by itself, but also blocked the inhibition by ADSC-CM. The resorption rate was reduced by ADSC-CM. The number of live birth/dam and the survival rate of pup at 1 week-old were both increased by ADSC-CM in mice with endometriosis. IPA demonstrated that PTX3 was potentially critical for the inhibition of endometriosis by ADSC-CM due to its anti-inflammatory and antiangiogenic properties as well as its importance in implantation. Conclusion: ADSC-CM inhibited endometriosis development and improved pregnancy outcomes in mice. Potential translation to clinical treatment for human endometriosis is expected.

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Condition tags

mesh:D004715endometriosischronic_pelvic_pain

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Intercellular Adhesion Molecule-1 Intercellular Adhesion Molecule-1 Intercellular Adhesion Molecule-1 Intercellular Adhesion Molecule-1 Intercellular Adhesion Molecule-1 Intercellular Adhesion Molecule-1 Intercellular Adhesion Molecule-1 Intercellular Adhesion Molecule-1 Intercellular Adhesion Molecule-1

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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