Autologous stem cells for personalised medicine

Developmental Biology Unit, UCL Institute of Child Health, London WC1N 1EH, UK.
New Biotechnology (Impact Factor: 2.9). 04/2012; 29(6):641-50. DOI: 10.1016/j.nbt.2012.04.002
Source: PubMed


Increasing understanding of stem cell biology, the ability to reprogramme differentiated cells to a pluripotent state and evidence of multipotency in certain adult somatic stem cells has opened the door to exciting therapeutic advances as well as a great deal of regulatory and ethical issues. Benefits will come from the possibility of modelling human diseases and develop individualised therapies, and from their use in transplantation and bioengineering. The use of autologous stem cells is highly desirable, as it avoids the problem of tissue rejection, and also reduces ethical and regulatory issues. Identification of the most appropriate cell sources for different potential applications, development of appropriate clinical grade methodologies and large scale well controlled clinical trials will be essential to assess safety and value of cell based therapies, which have been generating much hope, but are by and large not yet close to becoming standard clinical practice. We briefly discuss stem cells in the context of tissue repair and regenerative medicine, with a focus on individualised clinical approaches, and give examples of sources of autologous cells with potential for clinical intervention.

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    • "Adult multipotent stem/progenitor cells are promising cell sources for tissue repair and regeneration because of their self-renewal, differentiation capacity, and secretion of trophic factors [1]. Though developmentally not as versatile as embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), adult stem/progenitor cells represent a more clinically relevant cell source for regenerative medicine due to less ethical and/or safety issues [2]. In particular, mesenchymal stem/stromal cells (MSCs) and MSC-like multilineage precursor cells, including adipose-derived stem cells (ADSCs), mesoangioblasts, and multipotent adult progenitor cells (MAPCs), have attracted significant clinical attentions, largely owing to their accessibility as well as the robust trophic and immunosuppressive functions. "
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    ABSTRACT: Mesenchymal stem/stromal cells (MSCs) represent a promising adult progenitor cell source for tissue repair and regeneration. Their mysterious identity in situ has gradually been unveiled by the accumulating evidence indicating an association between adult multipotent stem/progenitor cells and vascular/perivascular niches. Using immunohistochemistry and fluorescence-activated cell sorting, we and other groups have prospectively identified and purified subpopulations of multipotent precursor cells associated with the blood vessels within multiple human organs. The three precursor subsets, myogenic endothelial cells (MECs), pericytes (PCs), and adventitial cells (ACs), are located, respectively, in the three structural tiers of typical blood vessels: intima, media, and adventitia. MECs, PCs, and ACs have been extensively characterized in prior studies and are currently under investigation for their therapeutic potentials in preclinical animal models. In this review, we will briefly discuss the identification, isolation, and characterization of these human blood-vessel-derived stem cells (hBVSCs) and summarize the current status of regenerative applications of hBVSC subsets.
    Full-text · Article · Aug 2015 · Stem cell International
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    • "A variety of endogenous stem cells have been found to participate in skin wound healing (Daley 2012; Plikus et al. 2012; Prasongchean and Ferretti 2012). However the anatomical distribution, morphology, and intracellular molecular arrangements of different SCs during skin healing in vivo cannot be readily assessed by flow cytometry and are not well defined. "
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    ABSTRACT: Various types of endogenous stem cells (SCs) participate in wound healing in the skin at different anatomical locations. SCs need to be identified through multiple markers, and this is usually performed using flow cytometry. However, immunohistological identification of endogenous stem cells in the skin at different anatomical locations by co-staining multiple SC markers has been seldom explored. We examined the immunohistological localization of four major types of SCs in wounded skin by co-staining for their multiple markers. Hematopoietic SCs were co-stained for Sca1 and CD45; mesenchymal SCs for Sca1, CD29, and CD106; adipose SCs for CD34, CD90, and CD105; and endothelial progenitor cells and their differentiated counterparts were co-stained for CD34, Tie2, and von Willebrand factor. We found Sca1(+)CD45(+) SCs in the epidermis, dermis and hypodermis of wounded skin. Sca1(+)CD29(+) and Sca1(+)CD106(+) mesenchymal SCs, CD34(+)CD105(+), CD34(+)CD90(+), and CD90(+)CD105(+) adipose SCs, as well as CD34(+)Tie2(+) endothelial progenitor cells were also located in the epidermis, dermis, and hypodermis. This study demonstrates the feasibility of using immunohistological staining to determine the location of SCs in wounded skin and the intracellular distribution of their molecular markers.
    Full-text · Article · Jan 2014 · Journal of Histochemistry and Cytochemistry
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    • "For more than a decade, MSC has been a highly promising stem cell source and extensively investigated for its therapeutic potentials [3, 4]. Unlike embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), MSCs are inherently more relevant to clinical applications due to the lack of ethical and safety issues, despite lower developmental versatility [5]. MSCs and similar mesodermal stem/progenitor cells have been shown to repair and/or regenerate a wide variety of damaged/defective organs, including bone, cartilage, muscle, heart, and skin [6–10]. "
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    ABSTRACT: Mesenchymal stem/stromal cells (MSCs) and MSC-like multipotent stem/progenitor cells have been widely investigated for regenerative medicine and deemed promising in clinical applications. In order to further improve MSC-based stem cell therapeutics, it is important to understand the cellular kinetics and functional roles of MSCs in the dynamic regenerative processes. However, due to the heterogeneous nature of typical MSC cultures, their native identity and anatomical localization in the body have remained unclear, making it difficult to decipher the existence of distinct cell subsets within the MSC entity. Recent studies have shown that several blood-vessel-derived precursor cell populations, purified by flow cytometry from multiple human organs, give rise to bona fide MSCs, suggesting that the vasculature serves as a systemic reservoir of MSC-like stem/progenitor cells. Using individually purified MSC-like precursor cell subsets, we and other researchers have been able to investigate the differential phenotypes and regenerative capacities of these contributing cellular constituents in the MSC pool. In this review, we will discuss the identification and characterization of perivascular MSC precursors, including pericytes and adventitial cells, and focus on their cellular kinetics: cell adhesion, migration, engraftment, homing, and intercellular cross-talk during tissue repair and regeneration.
    Full-text · Article · Aug 2013 · Stem cell International
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