Induction of Human Adipose-Derived Mesenchymal Stem Cells into Germ Lineage Using Retinoic Acid

Abstract

Accumulating evidence indicates that mesenchymal stem cells (MSCs) have been widely used in tissue engineering and regenerative medicine due to their multilineage differentiation potentials. Recent studies show that germ-like cells can also be derived from stem cells, such as human umbilical cord MSCs and human bone marrow MSCs in vitro. However, whether human adipose-derived MSCs (hAD-MSCs) can be induced into germ-like cells has never been reported. In this study, we isolated hAD-MSCs and confirmed that their characteristics were in accordance with that of MSCs established before. Germ cell lineage differentiation was performed by 10 μM retinoic acid (RA) treatment for 21 days. RA induction led to slender spindles and tadpole-like changes of cell morphology, and the expression of germ cell-specific markers (Oct4, Piwil2, Itgb1, SSEA-1, and Stra8) presented significant upregulation in the RA treatment group according to the polymerase chain reaction and immunofluorescence results. We first demonstrated that hAD-MSCs can differentiate into germ-like cells in vitro, which will provide theoretical and experimental basis for the clinical application of hAD-MSCs in the treatment for infertility.

Generation of male germ cells in vitro from the stem cells

“… 65 Human adipose-derived MSCs can also be induced into germ-like cells by RA. 66 RA is an important regulator of meiosis in gametogenesis, and it induces the expression of meiosis markers during spermatogenesis. 67 Growth factors, e.g ., LIF, GDNF, and EGF, contribute to the long-term culture of MSCs, whereas RA promotes germ cell differentiation of MSCs.…”

Adipose Derived Mesenchymal Stem Cells Restore Spermatogenesis in Male non Obstructive Azoospermia (Literature Review)

“…Successful spermatogenesis was achieved in guinea pigs with busulfan-induced azoospermia following injection of BM MSCs [113]. Allogenic AT MSCs could differentiate into cells similar to spermatogenic epithelium in vitro, providing theoretical and experimental background for clinical use of AT MSCs in treatment of infertility in animals such as guinea pigs with azoospermia [114]. In rats, BM MSCs mitigate the toxic effect of cisplatin on testes at both genetic and molecular levels [113].…”

Reprogramming Human Female Adipose Mesenchymal Stem Cells into Primordial Germ Cell-Like Cells

“…Similarly, male canine ASCs, differentiated into EBs or grown in monolayers, were induced into PGCLCs and putative gonocytes by BMP4 [ 16 ] or overexpression of CD61 (integrin-β3) via TGF-β [ 17 ]. Finally, human male ASCs treated with BMP4 or transfected with miR-106b gave rise to PGCLCs [ 18 ] or more advanced germ-like cells expressing OCT4 , PIWIL2 , ITGB1 , SSEA-1 and STRA8 , following 21 days of culture in the presence of RA [ 19 ].…”