Chondrogenic and Adipogenic Potential of Microvascular Pericytes

Abstract

Background-Previous studies have shown that pericytes can differentiate into osteoblasts and form bone. This study investigated whether pericytes can also differentiate into chondrocytes and adipocytes. Methods and Results-Reverse transcription-polymerase chain reaction demonstrated that pericytes express mRNA for the chondrocyte markers Sox9, aggrecan, and type II collagen. Furthermore, when cultured at high density in the presence of a defined chondrogenic medium, pericytes formed well-defined pellets comprising cells embedded in an extracellular matrix rich in sulfated proteoglycans and type II collagen. In contrast, when endothelial cells were cultured under the same conditions, the pellets disintegrated after 48 hours. In the presence of adipogenic medium, pericytes but not endothelial cells expressed mRNA for peroxisome proliferator-activated receptor-␥2 (an adipocyte-specific transcription factor) and incorporated lipid droplets that stained with oil red O. To confirm that pericytes can differentiate along the chondrocytic and adipocytic lineages in vivo, these cells were inoculated into diffusion chambers and implanted into athymic mice for 56 days. Accordingly, mineralized cartilage, fibrocartilage, and a nonmineralized cartilaginous matrix with lacunae containing chondrocytes were observed within these chambers. Small clusters of cells that morphologically resembled adipocytes were also identified. Conclusions-These data demonstrate that pericytes are multipotent cells that may contribute to growth, wound healing, repair, and/or the development and progression of various pathological states.

Pericytes, mesenchymal stem cells and their contributions to tissue repair

“…With regards to adipogenesis, Uezumi et al showed that PDGFRα+ MSCs, completely distinct from PDGFRβ+ pericytes, are responsible for adipogenesis in skeletal muscles and a balance between satellite cell-derived myofibres and PDGFRα+ cells maintain muscle homeostasis (Uezumi et al, 2010). However, differentiation of pericytes into adipocytes has been documented (Birbrair et al, 2013a;Farrington-Rock et al, 2004;Tang et al, 2008), and the differences between studies may well be dependent on the muscle condition and the subsequent interaction between cell types in the context of muscle injury.…”

“…In vitro tri-lineage differentiation of pericytes into mesenchymal cell types has been welldocumented (Crisan et al, 2012;Crisan et al, 2008;Farrington-Rock et al, 2004), and efforts to translate into in vivo transplantation models are underway. CD146+/CD34-/CD45-/CD56-pericytes from human skeletal tissue have exhibited osteo-, adipo-, chondro-and myogenic potential.…”

“…In brief, cultured MSC of a range of phenotypes have shown promise in combination with type II collagen hydrogel scaffolds and delivery of appropriate growth factors (Diaz-Flores et al, 2012). Pericytes isolated using culture-based methods from bovine retina (αSMA+) could be induced to an adipogenic and chondrogenic phenotype, exhibiting oil red O+ droplet formation and expression of PPAR-γ2 mRNA or demonstrating expression of aggrecan, type II collagen and sox2 mRNA, and secreting a type II collagenous matrix in vitro, respectively (Farrington-Rock et al, 2004). When injected into athymic mice via a diffusion chamber, mineralised and fibrocartilage were formed, suggestive of a cartilaginous matrix, and small clusters of adipocytes were identified morphometrically (Diaz-Flores et al, 2012;Farrington-Rock et al, 2004).…”

“…Pericytes isolated using culture-based methods from bovine retina (αSMA+) could be induced to an adipogenic and chondrogenic phenotype, exhibiting oil red O+ droplet formation and expression of PPAR-γ2 mRNA or demonstrating expression of aggrecan, type II collagen and sox2 mRNA, and secreting a type II collagenous matrix in vitro, respectively (Farrington-Rock et al, 2004). When injected into athymic mice via a diffusion chamber, mineralised and fibrocartilage were formed, suggestive of a cartilaginous matrix, and small clusters of adipocytes were identified morphometrically (Diaz-Flores et al, 2012;Farrington-Rock et al, 2004). This early study did not determine pericyte marker expression and therefore the pericyte subtypes involved are not clear, although the crude method of extraction suggests a rather heterogeneous population.…”

Cell Transplantation and “Stem Cell Therapy” in the Treatment of Myopathies: Many Promises in Mice, Few Realities in Humans

“…Pericytes are contractile cells that envelop the endothelial cells of capillaries and postcapillary venules [100]. Besides the function specifically linked to the vasculature, it was reported that they have oligopotential capacity, being able to differentiate into osteocytes, chondrocytes, and adipocytes [101,102]. Results on the myogenicity of pericytes are not homogeneous, varying from one laboratory to another.…”