Ontogeny and Multipotency of Neural Crest-Derived Stem Cells in Mouse Bone Marrow, Dorsal Root Ganglia, and Whisker Pad

Abstract

Although recent reports have described multipotent, self-renewing, neural crest-derived stem cells (NCSCs), the NCSCs in various adult rodent tissues have not been well characterized or compared. Here we identified NCSCs in the bone marrow (BM), dorsal root ganglia, and whisker pad and prospectively isolated them from adult transgenic mice encoding neural crest-specific P0-Cre/Floxed-EGFP and Wnt1-Cre/Floxed-EGFP. Cultured EGFP-positive cells formed neurosphere-like structures that expressed NCSC genes and could differentiate into neurons, glial cells, and myofibroblasts, but the frequency of the cell types was tissue source dependent. Interestingly, we observed NCSCs in the aorta-gonad-mesonephros region, circulating blood, and liver at the embryonic stage, suggesting that NCSCs migrate through the bloodstream to the BM and providing an explanation for how neural cells are generated from the BM. The identification of NCSCs in accessible adult tissue provides a new potential source for autologous cell therapy after nerve injury or disease.

RETRACTED ARTICLE: Mesenchymal stem cells and neural crest stem cells from adult bone marrow: characterization of their surprising similarities and differences

“…Remarkably, we failed to differentiate NCSC into smooth muscle cells. A couple of previous studies demonstrated that NCSC isolated from adult bone marrow could give rise to smooth muscle cells [6][7][8]. the genes belonging to this signaling pathway were the most up-regulated in NCSC clones and its inhibition decreased significantly their neuronal differentiation.…”

“…Several studies have already reported the presence of NCSC in adult bone marrow [6,8,9]. Those cells could be good candidates for use in cellular therapy approaches to improve symptoms in various neurological disorders, as they are able to differentiate into neural cells and are found in an easy-access location, allowing autologous graft procedures.…”

“…In such a model, the fate of NCC was mapped in vivo by mating ROSA26 Cre reporter (R26R) mice, expressing β-galactosidase upon Cre-mediated recombination, with mice expressing Cre recombinase under the control of the Wnt1 promoter. Using this transgenic model, Sieber-Blum and Grim demonstrated the presence of pluripotent neural crest-derived cells in adult hair follicles [4], Wong et al identified NCC in mouse adult skin [5] and Nagoshi et al isolated NCC from adult bone marrow [6]. Another mouse expressing the Cre recombinase under the control of the P0 promoter is also used in the same approach to map the NCC and, in the bone marrow, both Cre expressing mice have allowed to tag the same neural crest-derived cells [7][8][9].…”

Cell Therapy for Spinal Cord Injury by Neural Stem/Progenitor Cells Derived from iPS/ES Cells

“…However, this is a difficult problem, and although the task is urgent, it will be some time before it is possible to guarantee sufficient safety to enable stem cell use in clinical settings. Prior to any clinical trial of human CNS disorders using iPS cells, it will be essential to pre-evaluate each iPS cell clone carefully to be able to guarantee a safety level equal to other types of cells, such as hair follicle stem cells [45][46][47][48][49][50][51], multipotent skin-derived precursor cells [52,53], fetusderived neural stem/progenitor cells [54], and neural crest stem cells [55]. Moreover, experiments on primates will be essential, as preclinical studies before transplantation can be tried in SCI patients [56].…”

Stage- and area-specific control of stem cells in the developing nervous system

“…BMP signaling alone, on the other hand, instructively drives eNCSCs into the autonomic lineage in vitro [21], while in vivo BMP signaling regulates proliferation, differentiation and survival of NC-derived cells in a lineage specific fashion [22][23][24]. Cells with NCSC-like features can also be found in various postmigratory target structures of the neural crest, like in the embryonic sciatic nerve [25], adult skin [26,27], gut [28], adult dorsal root ganglia (DRG), whisker pad, and bone marrow [29]. However, such late stage NCSCs (e.g.…”