Msh homeobox 1 ()- and -overexpressing bone marrow-derived mesenchymal stem cells resemble blastema cells and enhance regeneration in mice.

Amputation of the proximal region in mammals is not followed by regeneration because blastema cells (BCs) and expression of regenerative genes, such as Msh homeobox () genes, are absent in this animal group. The lack of BCs and positional information in other cells is therefore the main obstacle to therapeutic approaches for limb regeneration. Hence, this study aimed to create blastema-like cells (BlCs) by overexpressing and genes in mouse bone marrow-derived mesenchymal stem cells (mBMSCs) to regenerate a proximally amputated digit tip. We transduced mBMSCs with and genes and compared osteogenic activity and expression levels of several -regulated genes (, , and keratin 14 ()) in BlC groups, including MSX1, MSX2, and MSX1/2 (in a 1:1 ratio) with those in mBMSCs and BCs and following injection into the amputation site. We found that gene overexpression increased expression of specific blastemal markers and enhanced the proliferation rate and osteogenesis of BlCs compared with mBMSCs and BCs via activation of and Histological analyses indicated full regrowth of digit tips in the -overexpressing groups, particularly in MSX1/2, through endochondral ossification 6 weeks post-injection. In contrast, mBMSCs and BCs formed abnormal bone and nail. Full digit tip was regenerated only in the MSX1/2 group and was related to boosted , and gene expression and to limb-patterning properties resulting from and overexpression. We propose that -transduced cells that can regenerate epithelial and mesenchymal tissues may potentially be utilized in limb regeneration.