MSCs are multipotent adult progenitor cells, which are capable of differentiating into various mesenchymal tissues, most prominently bone, cartilage and adipose. They were first isolated in 1974 from the bone marrow by Friedenstein and colleagues. Since then, MSCs have been isolated from a variety of other tissues, including adipose tissue, bone marrow and umbilical cord.
The International Society for Cellular Therapy (ISCT) has laid down several defining criteria for the identification of MSCs: 1) they must be plastic-adherent in standard culture conditions; 2) express the surface markers CD105, CD90 and CD73; 3) not express other lineage markers CD45 (pan-leukocyte), CD34 (hematopoietic and endothelial), CD14/CD11b (monocytic), CD79a/CD19 (B cell), or HLA class II; and 4) show the classical tri-lineage differentiation into osteoblasts, adipocytes and chondroblasts. Of note, MSCs are not a pure population of stem cells but exist as a heterogeneous, non-clonal mix of multipotent stem cells, committed progenitors and differentiated cells. This fact prompted a change in nomenclature from “mesenchymal stem cell” to “mesenchymal stromal cell”, though the terms are used interchangeably.
When tissues are damaged, MSCs are naturally released into the circulation, migrate to the site of injury1, and secrete molecules to create a microenvironment that promotes regeneration. Thus, the idea behind their therapeutic potential is that allogenically-transplanted MSCs can home to damaged tissue and act as a “drug store” to aid in recovery, or serve as an effector for tissue regeneration. Upon reaching the target tissue, MSCs secrete a variety of factors with powerful immune-modulating, angiogenic and anti-apoptotic effects. Accordingly, MSCs have been investigated for a wide breadth of clinical application and our lab has been evaluating them for the treatment of many diseases including diabetes islet transplantation kidney injury, Alzheimer’s disease and ARDS/COVID-19, to name a few2,3. We are also determining the molecular phenotype of MSCs from different sources, their ability to be delivered to different organs using locoregional approaches4, in addition to optimizing their therapeutic efficacy and homing/retention at target tissues by using pulsed focused ultrasound (pFUS)5.
- Ullah M, Liu DD, Thakor AS (2019). Mesenchymal Stromal Cell Homing: Mechanisms and Strategies for Improvement. iScience, 15, 421–438. PMID: 31121468; PMCID: PMC6529790.
- Ullah M, Liu DD, Rai S, Dadhania A, Jonnakuti S, Concepcion W, Thakor AS (2020). Reversing Acute Kidney Injury Using Pulsed Focused Ultrasound and MSC Therapy: A Role for HSP-Mediated PI3K/AKT Signaling. Molecular therapy. Methods & clinical development, 17, 683–694. PMID: 32346546; PMCID: PMC7177168.
- Ren G, Rezaee M, Razavi M, Taysir A, Wang J, Thakor AS (2019). Adipose tissue-derived mesenchymal stem cells rescue the function of islets transplanted in sub-therapeutic numbers via their angiogenic properties. Cell and tissue research, 376(3), 353–364. PMID: 30707291; PMCID: PMC6615057.
- Ng NN, Thakor AS (2020). Locoregional Delivery of Stem Cell-Based Therapies. Science Translational Medicine, 12(547). PMID: 32522806.
- Liu DD, Ullah M, Concepcion W, Dahl JJ, Thakor AS (2020). The role of ultrasound in enhancing mesenchymal stromal cell-based therapies. Stem cells translational medicine, 10.1002/sctm.19-0391. Advance online publication. PMID: 32157802.