November 30, 2020

The Niche

Knoepfler lab stem cell blog

Advanced Cell Technology (ACT) Revs Up Pre-Clinical Studies for MS

There is more good news from leading stem cell biotech Advanced Cell Technology (ACT) on preclinical rodent studies using stem cells to treat mice with an MS-like condition.ACT, Advanced Cell Technology

They published a new paper in the journal Stem Cell Reports entitled “Human ESC-Derived MSCs Outperform Bone Marrow MSCs in the Treatment of an EAE Model of Multiple Sclerosis” by Wang, et al.

Note added: there’s a related interesting paper from Jeanne Loring and Tom Lane’s groups in the same issue using neural progenitors made from hES cells. Update: there’s more reason for hope on stem cells for multiple sclerosis in 2020. See recent posts here.

Mesenchymal stem cells (MSCs) derived from human embryonic stem (hES) cells, termed hES-MSCs by the authors) were able to substantially reduce symptoms of a Multiple Sclerosis (MS)-like disease in mice.

While the control mice were severely disabled by the MS modeling condition including paralysis, those treated with the hES-MSCs were significantly healthier. In some cases this difference was dramatic as shown in the video above (Courtesy of Dr. Xiaofang Wang and Dr. Ren-he Xu, ImStem Biotechnology, Inc.) where we see a hES-MSC-treated MS model mouse running around and a control severely ill.

Interestingly, the transplantation of the hES-MSCs appeared to greatly aid the MS model mice even though all the injected cells died, suggesting an indirect mechanism through secretion of trophic factors. This notion was further supported by the fact that non-lethally irradiated (and hence non-mitotic) hESC-MSCs were still therapeutically beneficial.

HES-MSCs

They also demonstrate fairly convincingly that the hES-MSCs were better at aiding the mice than MSCs derived from bone marrow (BM-MSCs). This difference was traceable to the unique ability of hES-MSCs to readily extravasate (crawl through blood vessels) into the central nervous system (see Figure 6C above). The inability of BM-MSCs to do much therapeutic benefit may be linked to their secretion of high levels of IL-6.

This paper is exciting and important. As with pretty much all papers in the biomedical field, there are some limitations here as well and room for future studies to further clarify things. For example, there is a growing realization that for a number of conditions, especially those involving the inflammatory and immune-related illnesses such as MS, the unique physiology of mice may yield results not entirely translatable to humans. Further, more specifically the MS model here, called experimental autoimmune encephalitis (EAE), has some limitations as a model of MS in humans. Still, this work represents a significant advance and provides hope for future treatments of MS based on stem cells.

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