From the laboratory bench to the patient's bedside: An update on clinical trials with mesenchymal stem cells

Abstract

Mesenchymal Stem Cells (MSCs) are non-hematopoietic multi-potent stem-like cells that are capable of differentiating into both mesenchymal and non-mesenchymal lineages. In fact, in addition to bone, cartilage, fat, and myoblasts, it has been demonstrated that MSCs are capable of differentiating into neurons and astrocytes in vitro and in vivo. MSCs are of interest because they are isolated from a small aspirate of bone marrow and can be easily expanded in vitro. As such, these cells are currently being tested for their potential use in cell and gene therapy for a number of human diseases. Nevertheless, there are still some open questions about origin, multipotentiality, and anatomical localization of MSCs. In this review, we discuss clinical trials based on the use of MSCs in cardiovascular diseases, such as treatment of acute myocardial infarction, endstage ischemic heart disease, or prevention of vascular restenosis through stem cell-mediated injury repair. We analyze data from clinical trials for treatment of osteogenesis imperfecta (OI), which is a genetic disease characterized by production of defective type I collagen. We describe progress for neurological disease treatment with MSC transplants. We discuss data on amyotrophic lateral sclerosis (ALS) and on lysosomal storage diseases (Hurler syndrome and metachromatic leukodystrophy). A section of review is dedicated to ongoing clinical trials, involving MSCs in treatment of steroid refractory Graft Versus Host Disease (GVHD); periodontitis, which is a chronic disease affecting periodontium and causing destruction of attachment apparatus, heart failure, and bone fractures. Finally, we will provide information about biotech companies developing MSC therapy.

Mesenchymal Stem Cells Are Recruited into Wounded Skin and Contribute to Wound Repair by Transdifferentiation into Multiple Skin Cell Type

“…MSCs can be considered nonhemopoietic multipotent stem-like cells that are capable of differentiating into both mesenchymal and nonmesenchymal lineages (33). However, there is no specific single marker to clearly define MSCs.…”

“…In fact, at present, MSCs are identified through a combination of physical, phenotypic, and functional properties. The classical assay used to identify MSCs is the colony forming unit assay that identifies adherent spindle shaped cells that proliferate to form colonies and can be induced to differentiate into adipocytes, osteocytes, and chondrocytes (33). Because MSC in our study qualify this criteria, we used the term "mesenchymal stem cells" in this article.…”

Derivation and immunological characterization of mesenchymal stromal cells from human embryonic stem cells

“…Nevertheless, interest in MSCs has already moved from in vitro and animal studies into actual clinical trials in patients [36]. Several phase I-II clinical trials have already shown the safety and efficacy of BM-derived MSCs for enhancing the engraftment of co-transplanted HSCs in patients with hematologic and non-hematologic malignancies [37,38].…”

Osteoblast-induced EGFR/ERBB2 signaling in androgen-sensitive prostate carcinoma cells characterized by multiplex kinase activity profiling

“…Non-hematopoietic stem cells in the bone marrow are capable of differentiating into a variety of tissue entities, including osteogenic cells of bone tissue [29]. Incubation of mononuclear cells isolated from adult, human bone marrow with mesenchymal stem cell-stimulating medium followed by osteogenic differentiation medium [6,7] gave rise to cells with osteoblastic characteristics, for example mineral deposition (Fig.…”