Enhancing the efficacy of mesenchymal stem cell therapy

Abstract

Mesenchymal stem cell (MSC) therapy is entering a challenging phase after completion of many preclinical and clinical trials. Among the major hurdles encountered in MSC therapy are inconsistent stem cell potency, poor cell engraftment and survival, and age/disease-related host tissue impairment. The recognition that MSCs primarily mediate therapeutic benefits through paracrine mechanisms independent of cell differentiation provides a promising framework for enhancing stem cell potency and therapeutic benefits. Several MSC priming approaches are highlighted, which will likely allow us to harness the full potential of adult stem cells for their future routine clinical use.

Keywords: Clinical trial; Mesenchymal stem cell; Paracrine; Therapy.

Figure 1

Ex vivo expansion of mesenchymal stem cells reduces expression of growth factor/cytokine genes. Porcine mesenchymal stem cells (MSCs) were expanded as described[42]. Threshold cycle (C_T) for the illustrated genes was determined by real-time reverse transcription polymerase chain reaction. Early and late passage MSCs received less than 5 and more than 10 trypsin passages, respectively. ^aP < 0.05, ^bP < 0.01 vs arly passage MSCs.

Figure 2

Intramuscular administration of mesenchymal stem cells mediates a paracrine mechanism of distal organ repair. The paracrine cascade initiated by mesenchymal stem cells (MSCs) is illustrated by blue arrows. TLR3 priming by poly (I:C) generates a super MSC phenotype through amplification of paracrine factors, which enhances MSC potency for cardiac repair (indicated by triple green plus signs). Supporting data have been published[6,30,31,45,126].