Potential conversion of adult clavicle‐derived chondrocytes into neural lineage cells in vitro

Abstract

Neural stem cells (NSC) can be isolated from a variety of adult tissues and become a valuable cell source for the repair of peripheral and central nervous diseases. However, their origin and identity remain controversial because of possible de-differentiation/trans-differentiation or contaminations by hematopoietic stem cells (HSCs) or mesenchymal stem cells (MSCs). We hypothesize that the commonly used NSC culture medium can induce committed cartilage chondrocytes to de-differentiate and/or trans-differentiate into neural cell lineages. Using a biological isolation and purification method with explants culture, we here show that adult rat clavicle cartilage chondrocytes migrate out from tissue blocks, form sphere-like structures, possess the capability of self-renewal, express nestin and p75NTR, markers for neural crest progenitors, and differentiate into neurons, glia, and smooth muscle cells. Comparing with adult cartilage, the spherical-forming neural crest cell-like cells downregulate the chondrocytic marker genes, including collagen II, collagen X, and sox9, as well as neural-lineage repressors/silencers REST and coREST, but upregulate a set of well-defined genes related to neural crest cells and pro-neural potential. Nerve growth factor (NGF) and glial growth factor (GGF) increase glial and neuronal differentiation, respectively. These results suggest that chondrocytes derived from adult clavicle cartilage can become neural crest stem-like cells and acquire neuronal phenotypes in vitro. The possible de-differentiation/trans-differentiation mechanisms underlying the conversion were discussed.

Collagens in the developing and diseased nervous system

“…The specific localization of collagen II in the neural tube suggests that it could be involved in neuroblast differentiation. No more is known about this, but since recent data argue for the possible transdifferentiation of adult mesenchymal cells into neural cells [79,80], knowing if there is a specific cell type secreting collagen II during brain development might be a relevant issue.…”

Comparison of equine tendon-, muscle-, and bone marrow–derived cells cultured on tendon matrix

“…The most prominent avenues of investigation with MSCs have been directed at repair of bone, cartilage, myocardium, and CNS tissues. [14][15][16][17] Isolation of a homogeneous population of progenitor cells from bone marrow is time-consuming, and there is much variation in cell numbers, cell viability, and growth rates among samples. 18,19 More recent studies 20,21 indicate that alternative sources of progenitor cells (eg, fat, synovium, cartilage, and satellite cells) might also be beneficial for specific therapeutic applications.…”

Intravenous C16 and angiopoietin-1 improve the efficacy of placenta-derived mesenchymal stem cell therapy for EAE

“…C16 and Ang-1 boosted the ability of the engrafted PMSCs to differentiate down the neuronal–glial lineage as assessed by the expression of the neuronal–glial markers NF-200 and MBP in these cells. Moreover, C16 and Ang-1 upregulated BDNF (a key player in neuron survival and differentiation 22 , 23 ), GAP-43 (a driving factor of axonal sprouting and restoration 24 , 25 ), and p75NTR (a regulator of neuron proliferation and maturation 31 , 32 ) and downregulated the apoptosis marker caspase-3 in the engrafted PMSCs. Invasion of inflammatory cells into MSC grafts is considered to negatively impact the survival and function of the grafted cells 12 .…”