Hurdles to uptake of mesenchymal stem cells and their progenitors in therapeutic products

Abstract

Twenty-five years have passed since the first clinical trial utilising mesenchymal stomal/stem cells (MSCs) in 1995. In this time academic research has grown our understanding of MSC biochemistry and our ability to manipulate these cells in vitro using chemical, biomaterial, and mechanical methods. Research has been emboldened by the promise that MSCs can treat illness and repair damaged tissues through their capacity for immunomodulation and differentiation. Since 1995, 31 therapeutic products containing MSCs and/or progenitors have reached the market with the level of in vitro manipulation varying significantly. In this review, we summarise existing therapeutic products containing MSCs or mesenchymal progenitor cells and examine the challenges faced when developing new therapeutic products. Successful progression to clinical trial, and ultimately market, requires a thorough understanding of these hurdles at the earliest stages of in vitro pre-clinical development. It is beneficial to understand the health economic benefit for a new product and the reimbursement potential within various healthcare systems. Pre-clinical studies should be selected to demonstrate efficacy and safety for the specific clinical indication in humans, to avoid duplication of effort and minimise animal usage. Early consideration should also be given to manufacturing: how cell manipulation methods will integrate into highly controlled workflows and how they will be scaled up to produce clinically relevant quantities of cells. Finally, we summarise the main regulatory pathways for these clinical products, which can help shape early therapeutic design and testing.

GMP Compliant Production of a Cryopreserved Adipose-Derived Stromal Cell Product for Feasible and Allogeneic Clinical Use

“…Application of MSCs has emerged as a promising tool for regenerative medicine, as the efficacy of MSC-based cell therapy has been demonstrated for a broad spectrum of diseases [ 2 , 40 ]. ASCs have gained attention, as they can be isolated from AT at a relatively high yield and expanded extensively in vitro .…”

Recent Trends in Multipotent Human Mesenchymal Stem/Stromal Cells: Learning from History and Advancing Clinical Applications

“…Thus, a single MSC colony can give rise to different cell types with varied differentiation potentials. With publication of different data sets, it has been theorized that even within MSC populations, cells exist in a hierarchical structure, with some remaining as unipotential or dipotential whilst others become multipotential, a characteristic which they can eventually loose [118][119][120][121]. Several pieces of evidence suggest that the transformation of MSCs may be linked to a lower proliferation rate and decreased expression of markers such as CD146 [122][123][124].…”

Novel Therapeutic Trends in Pneumonia: Antibiotics and Mesenchymal Stem Cells

“…Due to the challenging manufacturing processes and limited availability of MSCs, the current cost of MSCs is quite expensive, varying from $15,000 to $30,000 per 1-5 million cGMP-MSCs per kilogram [66]. Improvements in cell expansion technologies to make MSC treatments more readily available and cost-effective need to continue to develop for MSC treatments to become a viable treatment option for pneumonia [67].…”