Evaluation of safety, feasibility and efficacy of intra-ovarian transplantation of autologous adipose derived mesenchymal stromal cells in idiopathic premature ovarian failure patients: non-randomized clinical trial, phase I, first in human

被引：48

作者：

Mashayekhi, M. ^{[1
]}

Mirzadeh, E. ^{[2
]}

Chekini, Z. ^{[1
]}

Ahmadi, F. ^{[3
]}

Eftekhari-Yazdi, P. ^{[4
]}

Vesali, S. ^{[5
]}

Madani, T. ^{[1
]}

Aghdami, N. ^{[2
]}

机构：

[1] ACECR, Royan Inst Reprod Biomed, Reprod Biomed Res Ctr, Dept Endocrinol & Female Infertil, POB 16635-148,Royan Allay,Eastern Hafez St, Tehran, Iran

[2] ACECR, Royan Inst Stem Cell Biol & Technol, Cell Sci Res Ctr, Dept Regenerat Med, POB 16635-148,Shaghayegh Alley,Banihashem Sq, Tehran, Iran

[3] ACECR, Royan Inst Reprod Biomed, Reprod Biomed Res Ctr, Dept Reprod Imaging, Tehran, Iran

[4] ACECR, Royan Inst Reprod Biomed, Reprod Biomed Res Ctr, Dept Embryol, Tehran, Iran

[5] ACECR, Royan Inst Reprod Biomed, Reprod Epidemiol Res Ctr, Dept Diabet Obes & Metab, Tehran, Iran

来源：

JOURNAL OF OVARIAN RESEARCH | 2021年 / 14卷 / 01期

关键词：

Adipose derived mesenchymal stromal cell; FSH; Premature ovarian failure; Return menstruation; Ovarian volume;

D O I：

10.1186/s13048-020-00743-3

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background Premature ovarian failure (POF) is characterized by the loss of ovarian activity before the age of 40 years. Stem cell therapy has the capability to create a regenerative microenvironment and is a proposed treatment for POF-related infertility due to the presence of renewal folliculogenesis and germ cells in the adult ovaries. In this study, we assessed the safety, feasibility, efficacy and dose adjustment of autologous adipose-derived stromal cells (ADSCs) and their ability to improve ovarian function in POF patients. Methods This study was a non-randomized clinical trial, phase I. Nine women with a definitive diagnosis of POF were divided into three groups (n = 3 per group) that received either 5 x 10(6), 10 x 10(6), or 15 x 10(6) autologous ADSCs suspension transplanted in the one ovary. Participants were followed-up at 24 h after the transplantation, and at 1 and 2 weeks, and 1, 2, 3, 6, and 12 months after the transplantation. The primary objective was to evaluate the safety of ADSCs transplantation. Secondary objectives included the effects of ADSCs transplantation on the resumption of menstruation, hormones level (Follicle-stimulating hormone (FSH) and anti-Mullerian hormone), ovarian function (Antral follicle count and ovary volume by ultrasonography evaluation) as well as dose escalation. Results Participants had not shown any early-onset possible side effects and secondary complications during follow-up. The menstruation resumption was observed in four patients which established for several months. In the 15 x 10(6) group, two POF patients had a return of menstruation second months after the intervention. Two other POF patients in 5 x 10(6) and 10 x 10(6) cell groups reported menstruation resumption at 1 month after the intervention. We observed decreased serum FSH levels of less than 25 IU/l in four patients. In two patients in 5 x 10(6) and 10 x 10(6) cell groups, serum FSH showed an inconsistent decline during a 1 year follow up after ADSCs transplantation. The ovarian volume, AMH, and AFC were variable during the follow-up and no significant differences between cell groups (p > 0.05). Conclusions We showed the intra-ovarian embedding of ADSCs is safe and feasible and is associated with an inconsistent decline in serum FSH. This should be further investigated with a large RCT.

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