Both multipotent adult progenitor cells and mesenchymal stromal cells are bone-marrow derived, non-hematopoietic adherent cells, that are well-known for having immunomodulatory and pro-angiogenic properties, whilst being relatively non-immunogenic. The authors compare the phenotypic and functional properties of these two cell types, to help in determining which would be the superior cell type for different applications.
Bone marrow stromal therapies are a very exciting field for research at present, with evidence showing a range of pleiotropic effects on immunomodulation, fibrosis, apoptosis, and angiogenesis. A summary of the key similarities and differences between MAPC and MSC are shown in Table 2.
Table 2. Summary of comparison of key characteristics between multipotent adult progenitor cells and mesenchymal stromal cells.
Evidence so far from hundreds of clinical trials suggests that MAPC and MSC both have a favorable safety profile. Nevertheless, the concern remains that because the cells’ activity is so dependent on surrounding stimuli, there is a possibility that they will have unpredictable side effects in vivo.
MSCs have been much more widely studied than MAPC. However, given the heterogeneity in cell types labeled as MSC, comparing study results is difficult. There are very few studies in which properties of MAPC and MSC have been directly compared in the same hands, using the same lab materials, such as culture media. Indeed, it may be possible that some of the trials using early-culture MSC, were in fact MAPC.
Whilst it is become clearer that MSC and MAPC are not truly immunologically privileged, their immune evasive nature gives these therapies particular advantage in acute conditions in which it may not be possible to predict the timing of the insult, and delays in delivery of cellular therapy could retract from its potential benefit. However, for use in cases such as bone transplantation, immune compatibility is more critical. A clear comparison of the efficacy of autologous vs. alloogeneic therapy in various clinical conditions is necessary. It would also be imperative to determine whether the negative impacts of IBMIR reaction can be overcome through use of low-passage cells, and what influence this has on the immunomodulatory activity of the remaining cells.
Whilst there is extensive in vitro and pre-clinical data supporting the efficacy of MSC and MAPC, the progress of therapy through clinical trials has been slow. There are relatively few clinical studies of MAPC, whilst hundreds of clinical trials are being performed for MSC with many of them have promising findings, the majority of these are phase I and II trials.
So far, data would suggest that the immunomodulatory and cytoprotective capacity of MAPC is equivalent to that of MSC, and that MAPC may have superior angiogenic and broader differentiation properties. In practical terms, MAPC offer the distinct advantage over classical MSC that they can be produced on a large scale, in a reproducible manner.
The use of cell-free preparations would be preferable to the administration of whole cells, and data with MSC suggests that this could be done without significant loss of efficacy. However, such data are not yet available for MAPC and in both cases, there is a need for good manufacturing practice guidelines for the large-scale production of MSC and MAPC derived products, such as exosomes.
The optimal dosing of both cellular therapies is unknown, and in clinical studies a large variation in dosing has been used. In a phase II clinical trial of patients with stroke, up to 1.2 billion cells were administered per patient (152), with no dose-related adverse effects. However, it would be important, for both cost-effectiveness of therapy and safety, to establish the minimum effective dose, which cannot be extrapolated from animal data.