Clinical Trials with Mesenchymal Stem Cells: An Update

Abstract

In the last year, the promising features of mesenchymal stem cells (MSCs), including their regenerative properties and ability to differentiate into diverse cell lineages, have generated great interest among researchers whose work has offered intriguing perspectives on cell-based therapies for various diseases. Currently the most commonly used adult stem cells in regenerative medicine, MSCs, can be isolated from several tissues, exhibit a strong capacity for replication in vitro, and can differentiate into osteoblasts, chondrocytes, and adipocytes. However, heterogeneous procedures for isolating and cultivating MSCs among laboratories have prompted the International Society for Cellular Therapy (ISCT) to issue criteria for identifying unique populations of these cells. Consequently, the isolation of MSCs according to ISCT criteria has produced heterogeneous, nonclonal cultures of stromal cells containing stem cells with different multipotent properties, committed progenitors, and differentiated cells. Though the nature and functions of MSCs remain unclear, nonclonal stromal cultures obtained from bone marrow and other tissues currently serve as sources of putative MSCs for therapeutic purposes, and several findings underscore their effectiveness in treating different diseases. To date, 493 MSCbased clinical trials, either complete or ongoing, appear in the database of the US National Institutes of Health. In the present article, we provide a comprehensive review of MSC-based clinical trials conducted worldwide that scrutinizes biological properties of MSCs, elucidates recent clinical findings and clinical trial phases of investigation, highlights therapeutic effects of MSCs, and identifies principal criticisms of the use of these cells. In particular, we analyze clinical trials using MSCs for representative diseases, including hematological disease, graft-versus-host disease, organ transplantation, diabetes, inflammatory diseases, and diseases in the liver, kidney, and lung, as well as cardiovascular, bone and cartilage, neurological, and autoimmune diseases.

Anti-apoptotic Effects of Human Wharton's Jelly-derived Mesenchymal Stem Cells on Skeletal Muscle Cells Mediated via Secretion of XCL1

“…[11][12][13] Recently numerous clinical trials have shown that naive human mesenchymal stem cells (MSCs) are safe and beneficial to be considered for design of treatment methods for various pathologies. [14][15][16] The primary mechanism of their therapeutic effects is via secretion of paracrine factors under abnormal and diseased cellular environments. For example, the paracrine action of human MSC has been demonstrated to prevent cell death and induce proliferation of endogenous progenitor cells.…”

Comparing the Effects of Human and Fetal Bovine Serum on Mesenchymal Stem Cells Under Oxidative Stress

“…MSCs, as one of the most studied type of stem cells, have proven their therapeutic effects in researches and clinical trials [3,[20][21][22][23]. Stem cell therapy often encounters reduced viability after implantation in the injured tissues.…”

“…Mesenchymal Stem Cells (MSCs) are under intense studies for clinical cell therapy because of their availability, immunosuppressive properties and ability to differentiate into many cell types [2][3][4][5]. MSCs, based on International Society for Cellular Therapy (ISCT) definition, should have three characteristics.…”

Mesenchymal Stem Cells and Platelet Derived Concentrates in Regenerative Medicine

“…These candidate cells have some common features, including the secretion of bioactive factors with a protein structure known as paracrine mechanism [20]. Paracrine factors secreted from MSCs contain a rich source of valuable bioactive factors, including angiogenesis-related factors, vascularization-specific factors, and neuroprotective factors [21].…”

“…According to evidence obtained from previous studies, MSC could be used to treat a variety of diseases, including hematological pathologies; Graft-versus-host disease (GvHD); cardiovascular disease; neurological disease; bone and cartilage disease; liver, lung, and kidney injuries;chronic inflammatory and autoimmune diseases; and urological disease [20,24].…”