Peak MSC-Are We There Yet?

Abstract

Human mesenchymal stem cells (hMSCs) are a critical raw material for many regenerative medicine products, including cell-based therapies, engineered tissues, or combination products, and are on the brink of radically changing how the world of medicine operates. Their unique characteristics, potential to treat many indications, and established safety profile in more than 800 clinical trials have contributed to their current consumption and will only fuel future demand. Given the large target patient populations with typical dose sizes of 10's to 100's of millions of cells per patient, and engineered tissues being constructed with 100's of millions to billions of cells, an unprecedented demand has been created for hMSCs. The fulfillment of this demand faces an uphill challenge in the limited availability of large quantities of pharmaceutical grade hMSCs for the industry-fueling the need for parallel rapid advancements in the biomanufacturing of this living critical raw material. Simply put, hMSCs are no different than technologies like transistors, as they are a highly technical and modular product that requires stringent control over manufacturing that can allow for high quality and consistent performance. As hMSC manufacturing processes are optimized, it predicts a future time of abundance for hMSCs, where scientists and researchers around the world will have access to a consistent and readily available supply of high quality, standardized, and economical pharmaceutical grade product to buy off the shelf for their applications and drive product development-this is "Peak MSC."

Keywords: bioprocessing; cell manufacturing; cell therapy; mesenchymal stem cell; regenerative medicine; stem cell.

Figure 1

PubMed articles associated with hMSC academic and preclinical research. The number of articles published each year that utilized hMSCs for in vitro and in vivo work in cell therapy (CE) and tissue engineering (TE) fields were totaled.

Figure 2

Estimated hMSC consumption per study in academic and preclinical research. The number of hMSCs consumed per in vitro and in vivo experiment were determined and used to calculate the amount of hMSCs consumed per publication for cell therapy and tissue engineering fields.

Figure 3

hMSC consumption in academic and preclinical research. The estimated yearly consumption of hMSCs for in vitro and in vivo work in publications from the cell therapy (CE) and tissue engineering (TE) fields was calculated based on the number of articles published per year and the amount of hMSCs consumed to generate the data required for publication.

Figure 4

Historical hMSC demand. The estimated yearly consumption of hMSCs from Clinical and Academic/Preclinical work. Clinical consumption was determined based on reported cell consumption from registered clinical trials and the total amount of registered trials each year (clinicaltrials.gov).

Figure 5

Trial total and patient number per trial by clinical phase. The total trials per clinical phase, the average patient number per trial per phase, and the total amount of patients per clinical phase were calculated based on currently registered clinical trials (clinicaltrials.gov).

Figure 6

Applications driving future hMSC consumption in 2040. The projected total number of hMSCs consumed per application and industry was determined by assumptions from historical clinical data, current consumption rates, and future projections based on the experiences and expertise of the authors.

Figure 7

Estimated MSC consumption in future commercial applications in 2040 at “Peak MSC.” The different types of applications requiring MSCs, how they will be consumed, and the total amounts of cells to be consumed were determined based on historical, current, and projected usage of MSCs as manufacturing technologies create an abundance of this critical raw material at “Peak MSC” in 2040.

Figure 8

Predicting the rise and fall of MSCs. The current, “peak,” and downfall stages of MSC demand are detailed with milestones over time (blue). Disruptive technologies (green) that are developing in parallel that have the potential to displace MSC demand are detailed over time. “Peak” MSC is predicted to occur in 2040.

Figure 9

Technology S-Curves and economics for hMSCs. hMSC production processes follow technology development S-Curves as they are adopted and integrated into products and processes. In general, a new hMSC production technology or method is developed, then achieves widespread adoption as a production platform and becomes a standard. This translates to a decrease in the total cost per cell produced due to efficiencies of scale. However, there are diminishing returns as larger scales are required and productivity plateaus until pioneering developments provide a breakthrough another production technology.

Figure 10

MSCs Are Having Their “Transistor Moment.” hMSCs are no different than technologies like transistors, as they are a highly technical and modular product that requires stringent control over manufacturing that can allow for high quality and consistent performance. MSCs therapeutic applicability is increasing exponentially, drawing parallels to computing. With enhanced economies of scale through improved manufacturing sciences, MSCs are primed for widespread usage as the “microchips” of tomorrow's RegenMed products.