Engrafted Bone Marrow-Derived Flk-1⁺Mesenchymal Stem Cells Regenerate Skin Tissue

Abstract

Stem cell plasticity has created great interest because of its potential therapeutic application in degenerative or inherited diseases. Transplantation of bone marrow-derived stem cells was shown to give rise to cells of muscle, liver, nerve, endothelium, epithelium, and so on. But there are still disputes about stem cell plasticity, especially concerning the contribution of bone marrow-derived cells to skin cells. In this study, CM-DiI fluorescence-labeled Flk-(1+) bone marrow mesenchymal stem cells (bMSCs) of BALB/c mice (H-2Kd, white) were transplanted into lethally irradiated C57BL/6 mice (H-2Kb, black). By fluorescence tracing, we found that donor cells could migrate and take residency at the skin, which was confirmed by Y chromosome-specific PCR and Southern blot. The recipient mice grew white hairs about 40 days later and white hairs could spread over the body. Immunochemistry staining and RT-PCR demonstrated that skin tissue within the white hair regions was largely composed of donor-derived H-2Kd cells, including stem cells and committed cells. Furthermore, most skin cells cultured from white hair skin originated from the donor. Thus, our findings provide direct evidence that bone marrow-derived cells can give rise to functional skin cells and regenerate skin tissue. These may have important scientific implications in stem cell biology and transplantation therapy for skin tissue injury.

Concise Review: Transplantation of Human Hematopoietic Cells for Extracellular Matrix Protein Deficiency in Epidermolysis Bullosa

“…Such cells may in turn release factors that operate on the host or that may differentiate into cells that directly participate in the wound healing process via release of C7 or other tissue repair proteins [39,40]. For example, both BM and CB grafts used in the clinical trial contain MSCs that are known to migrate to sites of injury including skin wounds [4,42,44,45]. There the MSCs engage in tissue healing, predominantly by secretion of paracrine factors, including appropriate extracellular matrix molecules, and by the recruitment of reparative cells from the recipient [34].…”

Efficient differentiation into skin cells of bone marrow cells recovered in a pellet after density gradient fractionation

“…Thereafter, many teams have provided compelling evidence indicating that bone marrow-derived cells can be converted into skin cells (31,(35)(36)(37). These studies demonstrated that not only whole bone marrow cells but also purified hematopoietic stem cells (6) and mesenchymal stem cells (31) can differentiate into skin cells.…”

Role of Adipose-Derived Mesenchymal Stem Cells in Full Thickness Wound Healing

“…The conclusion of this study was that perfect skin regeneration was achieved with MSCs after full-thickness wounds [3]. Also, the outcomes of Deng et al were promising, with the application of MSCs in mice transplanted into other irradiated mice [2]. They reported that bMSCs can contribute to skin functional cells and regeneration.…”

“…Mesenchymal stem cells have been used in several studies, which showed that regeneration of full-thickness wounds can be enhanced by application of MSCs [1][2][3][4]. For example, Bone Marrow derived Mesenchymal Stem Cells (bMSCs) have the potential to differentiate into osteoblasts, chondrocytes, myocytes [5][6][7][8], and adipocytes [2,5,7].…”