Scaffolds Protect Transplanted Stem Cells to Increase Therapeutic Benefit

One of the major areas of focus in regenerative research is finding ways to enhance the ability of transplanted cells to integrate with tissue, survive, and induce healing and growth. In early, first generation stem cell therapies, near all cells die quite quickly. The span of benefits that result is a reaction of native cells to the molecular signals briefly generated by the transplanted cells. The anti-inflammatory effects of mesenchymal stem cell therapies as presently practiced is a good example.

One way to improve cell survival is to build an artificial environment that to some degree mimics the extracellular matrix. Given that starting point, however, one can start adding additional features, such as molecular signals that enhance cell resilience, or structures that isolate cells for a time from hostile surroundings. Scaffolding materials are evolving to primarily provide protection for transplanted cells, rather than just a familiar three-dimensional structure.

A car accident leaves an aging patient with severe muscle injuries that won't heal. Treatment with muscle stem cells from a donor might restore damaged tissue, but doctors are unable to deliver them effectively. A new method may help change this. Researchers engineered a molecular matrix, a hydrogel, to deliver muscle stem cells called muscle satellite cells (MuSCs) directly to injured muscle tissue in patients whose muscles don't regenerate well. In lab experiments on mice, the hydrogel successfully delivered MuSCs to injured, aged muscle tissue to boost the healing process while protecting the stem cells from harsh immune reactions. The method was also successful in mice with a muscle tissue deficiency that emulated Duchenne muscular dystrophy.

Simply injecting additional muscle satellite cells into damaged, inflamed tissue has proven inefficient, in part because the stem cells encounter an immune system on the warpath. "Any muscle injury is going to attract immune cells. Typically, this would help muscle stem cells repair damage. But in aged or dystrophic muscles, immune cells lead to the release a lot of toxic chemicals like cytokines and free radicals that kill the new stem cells. "Our new hydrogel protects the stem cells, which multiply and thrive inside the matrix. The gel is applied to injured muscle, and the cells engraft onto the tissues and help them heal."

"Muscle satellite cells are resident stem cells in your skeletal muscles. They live on muscle strands like specks, and they're key players in making new muscle tissue. As we age, we lose muscle mass, and the number of satellite cells also decreases. The ones that are left get weaker. It's a double whammy. At a very advanced age, a patient stops regenerating muscle altogether. With this system we engineered, we think we can introduce donor cells to enhance the repair mechanism in injured older patients. We also want to get this to work in patients with Duchene muscular dystrophy."



The fact that transplanted stem cells all die is probably good. Since they still deliver benefits worry the risk of forming teratoma..

Posted by: Cuberat at August 22nd, 2018 8:24 AM

I'm wondering if scientists could borrow a trick from cancer and genetically engineering the muscle satellite cells to temporarily express PD-1L or otther immuno suppressants in response to a a small molecule drug.

Posted by: Jim at August 22nd, 2018 9:18 AM

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