Potential pre-activation strategies for improving therapeutic efficacy of mesenchymal stem cells: current status and future prospects

Abstract

Mesenchymal stem cell (MSC)-based therapy has been considered as a promising approach targeting a variety of intractable diseases due to remarkable multiple effect of MSCs, such as multilineage differentiation, immunomodulatory property, and pro-regenerative capacity. However, poor engraftment, low survival rate of transplanted MSC, and impaired donor-MSC potency under host age/disease result in unsatisfactory therapeutic outcomes. Enhancement strategies, including genetic manipulation, pre-activation, and modification of culture method, have been investigated to generate highly functional MSC, and approaches for MSC pre-activation are highlighted. In this review, we summarized the current approaches of MSC pre-activation and further classified, analysed the scientific principles and main characteristics of these manipulations, and described the pros and cons of individual pre-activation strategies. We also discuss the specialized tactics to solve the challenges in this promising field so that it improves MSC therapeutic functions to serve patients better.

Therapeutic potential of mesenchymal stromal/stem cells in critical‐care patients with systemic inflammatory response syndrome

“…overexpression of HIF‐1‐alpha, CXCR4 and IL‐10) 100 , 101 may enhance their immunomodulatory potential. 102 …”

“…In addition to standard MSCs production, different strategies (pre‐conditioning, cytokine or hypoxic priming) have been proposed to optimize MSCs therapy (increasing their homing, immunomodulatory capacities, paracrine production, lifespan and more durable effects). 102 , 116 Genetic modification has also been shown to enhance MSCs therapy for a higher production of regulatory factors or repair capacity. 116 Some of these strategies are also under clinical evaluation.…”

Stem cells for treatment of liver fibrosis/cirrhosis: clinical progress and therapeutic potential

“…Primary stem cells or unpretreated cells often fail to achieve the desired therapeutic effect due to poor homing ability, the very low survival rate after transplantation, and cellular senescence or decline in viability during in vitro culture. Enhancement strategies, including physiological microenvironment and pathological microenvironment to stimulate stem cell activation, have caused widespread concern [ 143 ]. A shift in the culture model is a common physiological way to enhance MSC.…”

Enhanced angiogenic potential of adipose-derived stem cell sheets by integration with cell spheroids of the same source

“…Comparing to the conventional monolayer culture, the three-dimensional (3D) culture system resembles the natural MSC microenvironment in vivo and provides enhanced cell–cell and cell–extracellular matrix (ECM) interactions, leading to improved biological functions of MSCs [ 7 ]. For example, cell sheet fabrication as a 3D culture technology has shown potential in their tissue regenerative effects [ 8 , 9 ].…”