Great Promise of Tissue-Resident Adult Stem/Progenitor Cells in Transplantation and Cancer Therapies

Department of Biochemistry and Molecular Biology, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Advances in Experimental Medicine and Biology (Impact Factor: 1.96). 01/2012; 741:171-86. DOI: 10.1007/978-1-4614-2098-9_12
Source: PubMed


Recent progress in tissue-resident adult stem/progenitor cell research has inspired great interest because these immature cells from your own body can act as potential, easily accessible cell sources for cell transplantation in regenerative medicine and cancer therapies. The use of adult stem/progenitor cells endowed with a high self-renewal ability and multilineage differentiation potential, which are able to regenerate all the mature cells in the tissues from their origin, offers great promise in replacing non-functioning or lost cells and regenerating diseased and damaged tissues. The presence of a small subpopulation of adult stem/progenitor cells in most tissues and organs provides the possibility of stimulating their in vivo differentiation, or of using their ex vivo expanded progenies for cell-replacement and gene therapies with multiple applications in humans without a high-risk of graft rejection and major side effects. Among the diseases that could be treated by adult stem cell-based therapies are hematopoietic and immune disorders, multiple degenerative disorders such as Parkinson's and Alzheimer's diseases, Types 1 and 2 diabetes mellitus as well as skin, eye, liver, lung, tooth and cardiovascular disorders. In addition, a combination of the current cancer treatments with an adjuvant treatment consisting of an autologous or allogeneic adult stem/progenitor cell transplantation also represents a promising strategy for treating and even curing diverse aggressive, metastatic, recurrent and lethal cancers. In this chapter, we reviewed the most recent advancements on the characterization of phenotypic and functional properties of adult stem/progenitor cell types found in bone marrow, heart, brain and other tissues and discussed their therapeutic implications in the stem cell-based transplantation therapy.

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    • "We speculate that under these conditions, it is possible that the secreted factors in the conditioned medium may provide the necessary survival and repair factors to recruit various cell types and to assist in the tissue repair process. In accordance with this idea, studies have shown that factors secreted from stem cells may be associated with vascular repair and regeneration.27,28 It is interesting to note that many of the identified factors secreted by human CD34+ cells are involved in cell survival and wound healing. "
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    ABSTRACT: Despite the progress in our understanding of genes essential for stem cell regulation and development, little is known about the factors secreted by stem cells and their effect on tissue regeneration. In particular, the factors secreted by human CD34+ cells remain to be elucidated. We have approached this challenge by performing a cytokine/growth factor microarray analysis of secreted soluble factors in medium conditioned by adherent human CD34+ cells. Thirty-two abundantly secreted factors have been identified, all of which are associated with cell proliferation, survival, tissue repair, and wound healing. The cultured CD34+ cells expressed known stem cell genes such as Nanog, Oct4, Sox2, c-Kit and HoxB4. The conditioned medium containing the secreted factors prevented cell death in liver cells exposed to liver toxin in vitro via inhibition of the caspase-3 signalling pathway. More importantly, in vivo studies using animal models of liver damage demonstrated that injection of the conditioned medium could repair damaged liver tissue (significant reduction in the necroinflammatory activity), as well as enable the animals to survive. Thus, we demonstrate that medium conditioned by human CD34+ cells has the potential for therapeutic repair of damaged tissue in vivo.Molecular Therapy (2013); doi:10.1038/mt.2013.194.
    Molecular Therapy 08/2013; 22(1). DOI:10.1038/mt.2013.194 · 6.23 Impact Factor
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    ABSTRACT: The search for more accessible mesenchymal stem cells than those found in bone marrow has propelled interest in dental tissues. Human dental stem/progenitor cells (collectively termed dental stem cells [DSCs]) that have been isolated and characterized include dental pulp stem cells, stem cells from exfoliated deciduous teeth, stem cells from apical papilla, periodontal ligament stem cells, and dental follicle progenitor cells. Common characteristics of these cell populations are the capacity for self-renewal and the ability to differentiate into multiple lineages. In vitro and animal studies have shown that DSCs can differentiate into osseous, odontogenic, adipose, endothelial, and neural-like tissues.
    Dental clinics of North America 07/2012; 56(3):549-61. DOI:10.1016/j.cden.2012.05.004
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    ABSTRACT: Embryonic stem (ES) cells have the potency to produce many cell types of the embryo and adult body. Upon transplantation into early host embryos, ES cells are able to differentiate into various specialized cells and contribute to host tissues and organs of all germ layers. Here we present data in the fish medaka (Oryzias latipes) that ES cells have a novel ability to form extra organs and even embryo-like miniatures. Upon transplantation as individual cells according to the standard procedure, ES cells distributed widely to various organ systems of three germ layers. Upon transplantation as aggregates, ES cells were able to form extra organs including the hematopoietic organ and contracting heart. We show that localized ES cell transplantation often led to the formation of extra axes that comprised essentially of either host cells or donor ES cells. These extra axes were associated with the head region of the embryo proper or formed at ectopic sites on the yolk sac. Surprisingly, certain ectopic axes were even capable of forming embryo-like miniatures. We conclude that ES cells have the ability to form entire organs and even embryo-like miniatures under proper environmental conditions. This finding points to a new possibility to generate ES cell-derived axes and organs.
    Stem cells and development 10/2012; 22(5). DOI:10.1089/scd.2012.0144 · 3.73 Impact Factor
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