Mesenchymal stem cells biological and biotechnological advances: Implications for clinical applications.

BACKGROUND: Mesenchymal stem cells (MSCs) are multipotent stem cells that are able to differentiate into multiple lineages including bone, cartilage, muscle and fat. They hold immunomodulatory properties and therapeutic ability to treat multiple diseases, including autoimmune and chronic degenerative diseases. In this article, we reviewed the different biological properties, applications and clinical trials of MSCs. Also, we discussed the basics of manufacturing conditions, quality control, and challenges facing MSCs in the clinical setting. METHODS: Extensive review of the literature was conducted through the databases PubMed, Google Scholar, and Cochrane. Papers published since 2015 and covering the clinical applications and research of MSC therapy were considered. Furthermore, older papers were considered when referring to pioneering studies in the field. RESULTS: The most widely studied stem cells in cell therapy and tissue repair are bone marrow-derived mesenchymal stem cells. Adipose tissue-derived stem cells became more common and to a lesser extent other stem cell sources e.g., foreskin derived MSCs. MSCs therapy were also studied in the setting of COVID-19 infections, ischemic strokes, autoimmune diseases, tumor development and graft rejection. Multiple obstacles, still face the standardization and optimization of MSC therapy such as the survival and the immunophenotype and the efficiency of transplanted cells. MSCs used in clinical settings displayed heterogeneity in their function despite their extraction from healthy donors and expression of similar surface markers. CONCLUSION: Mesenchymal stem cells offer a rising therapeutic promise in various diseases. However, their potential use in clinical applications requires further investigation.

BHLHA9 homozygous duplication in a consanguineous family: A challenge for genetic counseling.

Split-hand/foot malformation (SHFM) with long-bone deficiency (SHFLD) is a rare condition characterized by SHFM associated with long-bone malformation usually involving the tibia. It includes three different types; SHFLD1 (MIM % 119,100), SHFLD2 (MIM % 610,685) and SHFLD3 (MIM # 612576). The latter was shown to be the most commonly reported with a duplication in the 17p13.1p13.3 locus that was narrowed down to the BHLHA9 gene. Here, we report a consanguineous Lebanese family with three members presenting with limb abnormalities including tibial hemimelia. One of these patients presented with additional bowing fibula and another with bilateral split hand. CGH array analysis followed by RQ-PCR allowed us to detect the first homozygous duplication on the short arm of chromosome 17p13.3 including the BHLHA9 gene and involved in SHFLD3. Interestingly, one patient with the homozygous duplicated region, carrying thus four BHLHA9 copies presented with long bone deficiency but no SHFM. The incomplete penetrance and the variable expressivity of the disease in this family as well as the presence of the BHLHA9 homozygous duplication rendered genetic counseling extremely challenging and preimplantation genetic diagnosis almost impossible.