Amniotic fluid stem cells provide considerable advantages in epidermal regeneration: B7H4 creates a moderate inflammation microenvironment to promote wound repair

Abstract

The current treatments for severe skin injury all involve skin grafting. However, there is a worldwide shortage of donor skin tissue. In this study, we examined the advantages of using human amniotic fluid stem (hAFS) cells in skin wound healing. In vitro, hAFS cells differentiate into keratinocytes (termed hAFS-K). Like keratinocytes, hAFS-K cells express the markers K5, K14, K10 and involucrin; display typical cellular structure, including a tonofibril-rich cytoplasm; and construct a completely pluristratified epithelium in 3D culture. In vivo, in a mouse excisional wound model, GFP-positive hAFS cells participate in wound repair. Co-localization of GFP/K14 and GFP/K10 in the repaired epidermis demonstrated that hAFS cells can differentiate into keratinocytes. Real-time PCR results confirmed that hAFS cells can initiate and promote early-stage repair of skin damage. During wound repair, hAFS cells did not directly secrete repair-related factors, such as bFGF, VEGF, CXCL12, TGF-β1 and KGF, and provided a moderate inflammation reaction with lower expression of IL-1β, IL-6, TNF-α, Cox2 and Mac3. In hAFS cells, the negative co-stimulatory molecule B7H4 regulates low immunogenicity, which can provide a modest inflammatory reaction microenvironment for wound repair. Furthermore, with their uniquely high proliferation rate, hAFS cells offer a promising alternative for epidermal regeneration.

Concise Review: Amniotic Fluid Stem Cells: The Known, the Unknown, and Potential Regenerative Medicine Applications

“…Rodent AFSC closely resemble human AFSC in their growth properties and capacity for in vitro differentiation. Although expression of CD117 declines (and ultimately disappears) with this culture methodology [26], expression of some of the pluripotency (c-Myc, Oct-4, SSEA4) [36,37], endothelial (ETV2, FLI1), and all of the mesenchymal (CD29, CD44, CD73, CD90, CD105) markers is maintained [26]. Growth kinetics analysis of cultured AFSC has shown exponential growth, reaching up to 250 population doublings without any signs of slower proliferation or senescence [17,25,27].…”

In Utero Amniotic Fluid Stem Cell Therapy Protects Against Myelomeningocele via Spinal Cord Coverage and Hepatocyte Growth Factor Secretion

“…In this study, we clearly demonstrated that hAFSCs can cover the MMC defect and that some hAFSCs directly differentiate into cytokeratin-expressing cells, a main component of the skin epidermis. Previously, we and other groups reported that hAFSCs themselves and their secretomes can accelerate wound closure by enhancing reepithelialization using a dorsal excisional cutaneous wound model in BALB/c mice [20,32,33]. Furthermore, hAFSCs promote cutaneous wound closure through the direct differentiation into keratinocytes in vivo and have the potential to differentiate into epidermal-lineage cells including keratinocytes of various maturity levels in vitro [32].…”

“…Previously, we and other groups reported that hAFSCs themselves and their secretomes can accelerate wound closure by enhancing reepithelialization using a dorsal excisional cutaneous wound model in BALB/c mice [20,32,33]. Furthermore, hAFSCs promote cutaneous wound closure through the direct differentiation into keratinocytes in vivo and have the potential to differentiate into epidermal-lineage cells including keratinocytes of various maturity levels in vitro [32]. Based on these findings, our data indicated that hAFSCs attach to the surface of the spinal cord and cover the lesion with neoepidermal cells that directly differentiate from hAFSCs and promote epidermal ingrowth stimulated by some hAFSCs-derived paracrine mediators, leading to protection from the "second hit" during pregnancy.…”

The immunomodulatory function of human amniotic fluid stromal cells on B lymphocytes

“…They are easily accessible and readily available from amniocentesis samples that would otherwise be discarded. Besides the high proliferation capacity and differentiation potential, hAFSCs exhibit a low immunogenicity and immunoregulatory function [4]. Thus, hAFSCs possess considerable advantages that may render them useful for tissue engineering or in the treatment of various autoimmune diseases [4,5].…”

“…Our and many studies from other groups have confirmed that hAFSCs can be cultured in vitro through adherent growth; they have the features of rapid growth and a fibroblast-like appearance. hAFSCs have been identified to express the phenotypic markers of mesenchymal stromal cells (MSCs) [6][7][8], including CD29, CD44, OCT-4, and CD105; however, they negatively express human leukocyte antigen DR (HLA-DR) and the hematopoietic lineage marker CD34 [4,5,9]. MSCs have potent immunomodulatory properties and target the proliferation and differentiation of a variety of immune cells.…”