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  • One of the major challenges

    2018-10-22

    One of the major challenges to the application of MSCs to organ regeneration and repair in vivo has been cell delivery. Whilst it has been shown in some studies that MSCs delivered into the circulation can home to sites of damage, including sites of ischemic injury in the kidney, the mechanism of migration is still unclear and there is substantial loss of PR-619 manufacturer delivered via this approach (Kollar et al., 2009). To fulfil the promise of MSC-mediated tissue repair, it may therefore prove necessary to stimulate the endogenous organ-specific MSC populations. Our data on the patterns of differential gene expression between populations provide supporting evidence for a ‘memory of tissue origin’, highlighting a key gap in our understanding of CFU-F/MSC biology and the potential of these cells for tissue repair. Most notable here was the link between cCFU-F and key developmental transcriptional networks, including Mef2c and Isl1. Such tissue-specific signatures may be derivative of the stem cell or more differentiated components of the colonies. These may be related in evolutionary or ontological origin and share a common set of functions, yet nonetheless possess differentiative potential and/or cellular functions attuned to their specific roles in the tissue of origin. The other explanation for such differential gene expression in specific MSC populations would be contamination of the cultures with organ-specific cell types. The derivation of these MSC populations from CFU-F, followed by passaging, would make it unlikely that such residual heterogeneity is the primary cause of differential gene expression unless these ‘contaminating’ subpopulations were able to proliferate with a similar phenotype to MSCs. The functional pertinence of such tissue-specific phenotypes will require additional functional investigation, but may be critical to conferring organ-specific regenerative capacities on organ-specific populations.
    Materials and methods
    Acknowledgments This work was supported by the Australian Stem Cell Centre (grants to K.A., M.L, R.H. and S.G.), the Mater Medical Research Institute/Mater Foundation (KA) and NHMRC (AMR). The microarray research was supported by the Australian Research Council Special Research Centre for Functional and Applied Genomics (Institute for Molecular Bioscience) Microarray Facility. Technical assistance in immunophenotyping was provided by John Wilson and Virginia Nink from the Queensland Brain Institute Flow Cytometry Facility, University of Queensland. Further technical assistance was supplied by Robert Wadley. AMR is a Queensland Government Smart Futures Fellow. ML and SG are Research Fellows and RH is an Australia Fellow with the National Health and Medical Research Council, Australia.
    Introduction Skin is the largest organ and plays a key role in maintaining the body\'s homeostasis. One of the skin appendages, the hair follicle, is an easily accessible mini-organ with a number of important functions such as protection against cold, injuries and pathogens (Paus and Cotsarelis, 1999). The hair follicle undergoes numerous cycles of growth and retraction throughout the adult life, prompting scientists to hypothesize that this mini-organ might be a rich source of stem cells. However, the anatomic location where stem cells resided remained elusive until 1990 when Cotsarelis et al. first demonstrated that label-retaining cells resided in the bulge of the hair follicle (Cotsarelis et al., 1990), a finding that was later verified using transgenic mice (Morris et al., 2004; Tumbar et al., 2004). During the hair growth phase (anagen) bulge stem cells are activated and migrate to the base of the hair follicle, the bulb region, where they proliferate and differentiate to regenerate the inner and outer root sheath, matrix and hair shaft (Alonso and Fuchs, 2006). In addition to hair growth, bulge derived stem cells also contribute to epidermal regeneration in response to skin injury (Taylor et al., 2000). Interestingly, bugle stem cells exhibited robust multipotency as they could differentiate to multiple cell types including neurons, glia, keratinocytes and melanocytes (Amoh et al., 2005; Yu et al., 2010).