Improved therapeutics of modified mesenchymal stem cells: an update

Abstract

Background: Mesenchymal stromal cells (MSCs) have attracted intense interest due to their powerful intrinsic properties of self-regeneration, immunomodulation and multi-potency, as well as being readily available and easy to isolate and culture. Notwithstanding, MSC based therapy suffers reduced efficacy due to several challenges which include unfavorable microenvironmental factors in vitro and in vivo. Body: In the quest to circumvent these challenges, several modification techniques have been applied to the naïve MSC to improve its inherent therapeutic properties. These modification approaches can be broadly divided into two groups to include genetic modification and preconditioning modification (using drugs, growth factors and other molecules). This field has witnessed great progress and continues to gather interest and novelty. We review these innovative approaches in not only maintaining, but also enhancing the inherent biological activities and therapeutics of MSCs with respect to migration, homing to target site, adhesion, survival and reduced premature senescence. We discuss the application of the improved modified MSC in some selected human diseases. Possible ways of yet better enhancing the therapeutic outcome and overcoming challenges of MSC modification in the future are also elaborated. Conclusion: The importance of prosurvival and promigratory abilities of MSCs in their therapeutic applications can never be overemphasized. These abilities are maintained and even further enhanced via MSC modifications against the inhospitable microenvironment during culture and transplantation. This is a turning point in MSC-based therapy with promising preclinical studies and higher future prospect.

IL-1β Pretreatment Improves the Efficacy of Mesenchymal Stem Cells on Acute Liver Failure by Enhancing CXCR4 Expression

“…As a specific receptor of SDF-1, which is one of the most powerful chemokines, CXCR4 has been widely studied in the homing of various cells, including that of MSCs to the injured liver. Most of these studies confirmed the critical role of CXCR4 [21]. The Western blot results of this study showed that the expression of CXCR4 in Pre-MSCs was significantly increased compared to cells without IL-1β pretreatment, but the quantity of c-Met expression was constant.…”

“…As shown in the characterization experiments of cultured cells, the expression rates of CD90 and CD105 were greater than 95%, while those of CD45 and CD34 were less than 2%, and the good multidifferentiation potential was also verified. The efficacy of MSCs on ALF could be significantly improved by effective modification or pretreatment [10,21]. Although MSCs can differentiate into hepatocytes, recent studies have shown that microenvironment created by MSCs is the critical factor for their efficacy in improving the pathophysiological process of liver diseases [8].…”

“…The efficacy of MSCs on ALF could be significantly improved by effective modification or pretreatment [ 10 , 21 ]. Although MSCs can differentiate into hepatocytes, recent studies have shown that microenvironment created by MSCs is the critical factor for their efficacy in improving the pathophysiological process of liver diseases [ 8 ].…”

Therapeutic Evidence of Human Mesenchymal Stem Cell Transplantation for Cerebral Palsy: A Meta-Analysis of Randomized Controlled Trials

“…MSCs are attractive and promising because of their low immunogenicity, easy accessibility, and immunosuppressive potential in autologous transplantation [ 19 , 20 ]. However, the safety of stem cell therapy remains a top priority.…”

Gene Engineered Mesenchymal Stem Cells: Greater Transgene Expression and Efficacy With Minicircle Vs. Plasmid DNA Vectors in a Mouse Model of Acute Lung Injury

“…In contract, genetic modi cation of MSC may offer a more persistent bene cial effect compared to pre-treatment strategy. The overexpression or knockdown of speci c genes has been used to enhance MSC therapeutic potential by modulating survival, migration, adhesion and, regenerative and immunomodulatory effects (32).…”