More than 1050 clinical trials are registered at FDA.gov that explore multipotent mesenchymal stromal cells (MSCs) for nearly every clinical application imaginable, including neurodegenerative and cardiac disorders, perianal fistulas, graft-versus-host disease, COVID-19, and cancer. Several companies have or are in the process of commercializing MSC-based therapies. However, most of the clinical-stage MSC therapies have been unable to meet primary efficacy end points. The innate therapeutic functions of MSCs administered to humans are not as robust as demonstrated in preclinical studies, and in general, the translation of cell-based therapy is impaired by a myriad of steps that introduce heterogeneity. In this review, we discuss the major clinical challenges with MSC therapies, the details of these challenges, and the potential bioengineering approaches that leverage the unique biology of MSCs to overcome the challenges and achieve more potent and versatile therapies.

Hyperbranched polyglycerol is one of the most widely studied biocompatible dendritic polymer and showed promising applications. Here, we summarized the recent advancements in the field.

The introduction of cell-based therapies has provided new and unique strategies to treat many diseases and disorders including the recent approval of CAR-T cell therapy for the leukemia. Cell surface engineering is a methodology in which the cell surface is tailored to modulate cellular function and interactions. In addition to genetic engineering of cell surface proteins, a wide array of robust, innovative and elegant approaches have been developed to selectively target the cell surface. In this review, we will introduce the leading strategies currently used in cell surface engineering including broadly reactive chemical ligations and physical associations as well as more controlled approaches as demonstrated in genetic, enzymatic and metabolic engineering. Prominent applications of these strategies for cell-based therapies will be highlighted including targeted cell death, control over stem cell fate, immunoevasion, blood transfusion and the delivery of cells to target tissues. Advances will be focused specifically on cells which are the most promising in generating cell-based therapeutics including red blood cells, white blood cells (lymphocytes, macrophages), stem cells (multipotent and pluripotent), islet cells, cancer cells, and endothelial cells.