Evidence for Bone Marrow Adult Stem Cell Plasticity: Properties, Molecular Mechanisms, Negative Aspects, and Clinical Applications of Hematopoietic and Mesenchymal Stem Cells Transdifferentiation

Abstract

In contrast to the pluripotent embryonic stem cells (ESCs) which are able to give rise to all cell types of the body, mammalian adult stem cells (ASCs) appeared to be more limited in their differentiation potential and to be committed to their tissue of origin. Recently, surprising new findings have contradicted central dogmas of commitment of ASCs by showing their plasticity to differentiate across tissue lineage boundaries, irrespective of classical germ layer designations. The present paper supports the plasticity of the bone marrow stem cells (BMSCs), bringing the most striking and the latest evidences of the transdifferentiation properties of the bone marrow hematopoietic and mesenchymal stem cells (BMHSCs, and BMMSCs), the two BM populations of ASCs better characterized. In addition, we report the possible mechanisms that may explain these events, outlining the clinical importance of these phenomena and the relative problems.

Hematopoietic stem cells: An overview

“…Second, multiple tissue-specific stem cells (multipotent) are present in different organs and have the capability to de-differentiate to a less lineagecommitted state from where the cell can again start the program of differentiation to a more committed state (re-differentiation) [12]. For HSC trans-differentiation or reprogramming happen when they are exposed to a different microenvironment and changes its gene expression pattern to that of an alternative cell type [82]. Third, HSC may fuse with a non-hematopoietic cell (organ resident) to form a heterokaryon, thereby converting the gene expression pattern of the original BM cell type to that of the fusion partner [76].…”

“…BM hosts a variety of dedicated tissue-specific stem cells, such as muscle stem cells, neuronal stem cells, and hepatic progenitors. These stem cells may move from one tissue into another via the circulation and may be more plastic in early than in more differentiated stages [81,82].…”

“…Moreover in patients with MM, BM macrophages and mast cells transdifferentiate into endothelial cells thus contributing to vasculogenic mimicry. It is known that BM neovascularization contributes to MM progression [82].…”

Bone marrow-derived stem cells differentiate into retinal pigment epithelium-like cells in vitro but are not able to repair retinal degeneration in vivo

“…For both hypotheses, examples can be found in the literature [13,16] . Possible mechanisms underlying the plasticity of BMSCs have been summarized by Catacchio et al (2013) [6] . Therefore, the need for a final clarification of the details, especially the characterization of modulating factors, is a tedious nevertheless necessary task beyond the scope of this study.…”

“…New findings have recently contradicted the central dogmas of commitment of adult SC, including bone marrow-derived stem cells (BMSCs), by showing their plasticity to differentiate across tissue-lineage boundaries, irrespective of classical germ layer designations [6] . In this context transdifferentiation into non-hematopoietic, including retinal, cell types was documented [7][8][9] .…”