Functional Properties of Human-Derived Mesenchymal Stem Cell Spheroids: A Meta-Analysis and Systematic Review

Mesenchymal stem cells (MSC) are adult multi-potent cells that can be isolated from many types of tissues including adipose tissue, bone marrow, and umbilical cord. They show great potential for cell therapy-based treatments, which is why they are being used in numerous clinical trials for a wide range of diseases. However, the success of placebo-controlled clinical trials has been limited, so new ways of improving the therapeutic effects of MSC are being developed, such as their assembly in a 3D conformation. In this meta-analysis, we review aggregate formation, in vitro functional properties and in vivo therapeutic potential displayed by adipose tissue, bone marrow, and umbilical cord-derived MSC, assembled as spheroids. The databases PubMed and SciELO were used to find eligible articles, using free-words and MeSH terms related to the subject, finding 28 published articles meeting all inclusion and exclusion criteria. Of the articles selected 15 corresponded to studies using MSC derived from bone marrow, 10 from adipose tissue and 3 from umbilical cord blood or tissue. The MSC spheroids properties analyzed that displayed enhancement in comparison with monolayer 2D culture, are stemness, angiogenesis, differentiation potential, cytokine secretion, paracrine and immunomodulatory effects. Overall studies reveal that the application of MSC spheroids in vivo enhanced therapeutic effects. For instance, research exhibited reduced inflammation, faster wound healing, and closure, functional recovery and tissue repair due to immunomodulatory effects, better MSC engraftment in damaged tissue, higher MSC survival and less apoptosis at the injury. Still, further research and clinical studies with controlled and consistent results are needed to see the real therapeutic efficacy of MSC spheroids.