Analysis of Allogenicity of Mesenchymal Stem Cells in Engraftment and Wound Healing in Mice

Abstract

Studies have shown that allogeneic (allo-) bone marrow derived mesenchymal stem cells (BM-MSCs) may enhance tissue repair/regeneration. However, recent studies suggest that immune rejection may occur to allo-MSCs leading to reduced engraftment. In this study, we compared allo-BM-MSCs with syngeneic BM-MSCs or allo-fibroblasts in engraftment and effect in wound healing. Equal numbers of GFP-expressing allo-BM-MSCs, syngeneic BM-MSCs or allo-fibroblasts were implanted into excisional wounds in GFP-negative mice. Quantification of GFP-expressing cells in wounds at 7, 14 and 28 days indicated similar amounts of allogeneic or syngeneic BM-MSCs but significantly reduced amounts of allo-fibroblasts. With healing progression, decreasing amounts of allogeneic and syngeneic BM-MSCs were found in the wound; however, the reduction was more evident (2 fold) in allo-fibroblasts. Similar effects in enhancing wound closure were found in allogeneic and syngeneic BM-MSCs but not in allo-fibroblasts. Histological analysis showed that allo-fibroblasts were largely confined to the injection sites while allo-BM-MSCs had migrated into the entire wound. Quantification of inflammatory cells in wounds showed that allo-fibroblast- but not allo-BM-MSC-treated wounds had significantly increased CD45+ leukocytes, CD3+ lymphocytes and CD8+ T cells. Our study suggests that allogeneic BM-MSCs exhibit ignorable immunogenicity and are equally efficient as syngeneic BM-MSCs in engraftment and in enhancing wound healing.

Bone marrow mesenchymal stem cells enhance bone formation in orthodontically expanded maxillae in rats

“…6 Autologous MSCs have been investigated for the potential to regenerate a variety of tissues, 20,21 and studies also have confirmed that the use of allogeneic MSCs can efficiently repair bone and other tissue types in different animal models without provoking an adverse immune response. 14,22 In this study, we aimed to increase bone regeneration in the interpremaxillary suture using allogeneic BMSCs. This strategy has two advantages.…”

Advances in Hematopoietic Stem Cell Transplantation

“…Several studies suggest that MSCs are effective to treat aGVHD [48][49][50][51][52]. In experimental models MSCs modulate immune system through several mechanisms, including suppression of CD4 + and CD8 + T cell proliferation, induction of regulatory T cells, suppression of B cell differentiation and proliferation, release of soluble immunomodulatory factors and repair of damaged target organs [53][54][55][56][57]. However, little is known about MSCs effects on patients with GVHD.…”

Mesenchymal Stem Cells as Vehicles for Targeted Therapies

“…The absence of co-stimulatory molecules may lead to tolerance induction instead of rejection of allogeneic MSCs. The absence of host immune response against allogeneic MSCs has been demonstrated in vitro (Bartholomew et al, 2002;Di Nicola et al, 2002;Tse et al, 2003) and in vivo in animals (Atoui et al, 2008;Chen et al, 2009) and humans (Kebriaei et al, 2009;Le Blanc et al, 2004;Prasad et al, 2011;Sundin et al, 2007).…”