Hair Follicle Dermal Cells Support Expansion of Murine and Human Embryonic and Induced Pluripotent Stem Cells and Promote Haematopoiesis in Mouse Cultures

Abstract

In the hair follicle, the dermal papilla (DP) and dermal sheath (DS) support and maintain proliferation and differentiation of the epithelial stem cells that produce the hair fibre. In view of their regulatory properties, in this study, we investigated the interaction between hair follicle dermal cells (DP and DS) and embryonic stem cells (ESCs); induced pluripotent stem cells (iPSCs); and haematopoietic stem cells. We found that coculture of follicular dermal cells with ESCs or iPSCs supported their prolonged maintenance in an apparently undifferentiated state as established by differentiation assays, immunocytochemistry, and RT-PCR for markers of undifferentiated ESCs. We further showed that cytokines that are involved in ESC support are also expressed by cultured follicle dermal cells, providing a possible explanation for maintenance of ES cell stemness in cocultures. The same cytokines were expressed within follicles in situ in a pattern more consistent with a role in follicle growth activities than stem cell maintenance. Finally, we show that cultured mouse follicle dermal cells provide good stromal support for haematopoiesis in an established coculture model. Human follicular dermal cells represent an accessible and readily propagated source of feeder cells for pluripotent and haematopoietic cells and have potential for use in clinical applications.

Use of human intra-tissue stem/progenitor cells and induced pluripotent stem cells for hair follicle regeneration

“…DP and DS cells were shown to differentiate into hematopoietic, adipogenic, and osteogenic lineages [91, 92]. DP and DS cells supported embryonic stem cells and iPSC maintenance and hematopoiesis in vitro [93]. Furthermore, DS cells exhibited immunosuppressive role to improve islet allograft survival in the mouse model of type Ι diabetes [94].…”

CRISPR/Cas9 gene correction of HbH-CS thalassemia-induced pluripotent stem cells

“…The generation of patient-specific α-Thal-induced pluripotent stem cells (iPSCs) from patient somatic cells, the correction of disease-causing mutations in those cells, and differentiation into haematopoietic stem cells (HSCs) offer a new therapeutic strategy for this monogenic disease [7][8][9]. Recently, single-strand oligodeoxynucleotides (ssODNs), high-fidelity CRISPR/Cas9 nuclease and small molecules were used to achieve a seamless correction of the β-41/42 (TCTT) deletion mutation in β-thalassemia patient-specific iPSCs with remarkable efficiency [10].…”