A Brief Overview of Global Trends in MSC-Based Cell Therapy

Abstract

Human mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells or medicinal signaling cells, are important adult stem cells for regenerative medicine, largely due to their regenerative characteristics such as self-renewal, secretion of trophic factors, and the capability of inducing mesenchymal cell lineages. MSCs also possess homing and trophic properties modulating immune system, influencing microenvironment around damaged tissues and enhancing tissue repair, thus offering a broad perspective in cell-based therapies. Therefore, it is not surprising that MSCs have been the broadly used adult stem cells in clinical trials. To gain better insights into the current applications of MSCs in clinical applications, we perform a comprehensive review of reported data of MSCs clinical trials conducted globally. We summarize the biological effects and mechanisms of action of MSCs, elucidating recent clinical trials phases and findings, highlighting therapeutic effects of MSCs in several representative diseases, including neurological, musculoskeletal diseases and most recent Coronavirus infectious disease. Finally, we also highlight the challenges faced by many clinical trials and propose potential solutions to streamline the use of MSCs in routine clinical applications and regenerative medicine.

Keywords: Gene and Stem Cell Therapy; Personalized Medicine; Precision Medicine; Regenerative Medicine; Stem Cell Therapy; iPSC.

Fig. 1

Schematic illustration of MSC sources and four focusing areas. Along with immune cells, MSCs isolated from various tissues show immune modulating functions. MSCs heterogeneity, application of single cell RNA sequencing, and gene-editing are three proof of concepts used as advanced technologies in deciphering MSC uniqueness (central and right). Cell culture, expansion and biobanking are standard procedures to establish good laboratory practices for further use in clinical practice (left). The figure was prepared with BioRender

Fig. 2

Overview of registered MSC based clinical trial growth and cell source. A Line plot yearly registered mesenchymal stem cells-based clinicals trials at ClinicalTrials.gov since the first use in 1995 up to 2020. B Pie chart of number of clinical trials based on main sources used: BM-MSCs, UC-MSCs, AT-MSCs. 476 clinical trials did not disclose the sources of the MSCs, or the cells source is named as allogenic (61). Others refers to cells derived from tissue such as placenta, dental pulp, amniotic mesenchymal stem cells and other

Fig. 3

Overview of registered MSC-based clinical trial phase and status. A. Pie chart distribution of clinical trials according to investigation phases. B. Bar blot of clinical trials according to the study status. Notably, a large number of clinical trials are lacking updates on the progressing status. All data was obtained by July 14^th, 2021

Fig. 4

Overview of the number of registered participants for MSC-based clinical trials according to countries. Data was collected by July 14^th, 2021

Fig. 5

Overview of the administration and targeted diseases for MSC-based clinical trials. A. Four key administration (delivery) decision-determining are dosage, dose frequency, interval, and suspension method. Six administration routs and organs targeted by these clinical trials are highlighted. B. Overview of the types of diseases targeted by these registered clinical trials. Data collected by July 14^th,2021. For Pneumological disease, approximal half of the clinical trials are registered for treatment of COVID-19. Pie chart was shown to the right. Part A) was prepared using by BioRender