Induced Pluripotent Derived Neural Stem Cell Therapy Leads to Improved Recovery in a Pig Ischemic Stroke Model

Summary

Stroke is the number one cause of long-term disability in the United States and the second leading cause of death worldwide. Despite the significant effect of stroke on millions of patients and considerable effort to develop treatments, there are currently few therapies- all of which have major limitations. We have recently demonstrated that the transplantation of induced pluripotent stem cell derived neural stem cells (iNSCs) into the stroke brain region leads to improved metabolism, cerebral blood flow, decreased inflammation, and improvements in endogenous neural recovery mechanisms. In addition, iNSCs were capable of forming neuron and glia cell types to replace lost and damaged brain tissue. This cellular and tissue level improvement in stroke recovery lead to significant improvement in functional outcomes that will potentially translate to improved stroke patient recovery.

Situation

Stroke is the number one cause of long term disability and fifth leading cause of death in the United States. Despite over 700 drugs going to human clinical trials, only one pharmacological treatment with significant therapeutic short comings has been approved by the Food and Drug Administration. An assessment of failed treatments by the Stem Cell Therapies as an Emerging Paradigm in Stroke group, an assembly of leading stroke experts, has identified stem cell therapies as a promising option for the treatment of stroke patients. Induced pluripotent stem cell derived neural stem cells (iNSCs) have the ability to function as a dual therapeutic as they can produce regenerative signaling factors and replace damaged tissue. However, the efficacy of iNSC therapy has never been tested in a large animal stroke model similar to humans such as the recently developed pig stroke model.

Response

iNSCs have been recently developed and are a promising therapeutic cell type for neural injuries such as stroke. iNSCs can be derived from the patient’s own body limiting the potential for rejection. Our research team has found these cells to be highly proliferative and easy to maintain in culture making them amenable to therapy. In culture, these cells are capable of forming all three major neural cell types of the central nervous system (astrocytes, oligodendrocytes and neurons). Stroked pigs that received the iNSC therapy showed significant improvement in brain metabolism, cerebral blood flow, decreased inflammation, and increased endogenous neural stem cell activity. In addition, iNSCs were capable of forming neuron and glia cell types to replace lost and damaged brain tissue. Animals also showed improved motor function suggesting enhanced recovery.

Impact

The development of iNSC regenerative cell therapy will lead to the replacement and repair of damaged neural networks in stroke patients. This will lead to improved sensory, motor and cognitive function and improve the patient’s life quality. This platform technology can also be adapted to other central nervous system injuries such as spinal cord injuries or traumatic brain injury. This work has recently been published: 1) https://www.ncbi.nlm.nih.gov/pubmed/28855627 2) https://www.ncbi.nlm.nih.gov/pubmed/29761021 3) https://pubmed.ncbi.nlm.nih.gov/32194080/

State Issue

Health & Nutrition

Details

  • Year: 2020
  • Geographic Scope: International
  • County: Clarke
  • Location: College Station, Athens
  • Program Areas:
    • Agriculture & Natural Resources

Author

    West, Franklin Delano

Collaborator(s)

CAES Collaborator(s)

  • Duberstein, Kylee Jo
  • Kaiser, Erin Elizabeth
  • Kinder, Holly Ann
  • Stice, Steven L.

Non-CAES Collaborator(s)

  • Elizabeth Howerth
  • Hea Jin Park
  • Simon Platt
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Research Impact