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Human Brain Vascular Pericytes as a New Treatment for SCI?

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Review of “Early Intravenous Delivery of Human Brain Stromal Cells Modulates Systemic Inflammation and Leads to Vasoprotection in Traumatic Spinal Cord Injury” from Stem Cells Translational Medicine by Stuart P. Atkinson

Following the initial physical trauma of spinal cord injury (SCI), secondary inflammatory responses can worsen the injury and impede recovery. Mesenchymal stem cells (MSCs) are well-known for their inflammatory-dampening abilities [1] and so their transplantation may provide a means to improve recovery from SCI. However, variable preclinical results means that MSC effectiveness remains controversial in SCI [2] and there have been further questions surrounding the optimal source for MSCs.

In a new study in Stem Cells Translational Medicine, researchers from the laboratory of Michael Fehlings (University of Toronto, Canada) sought to assess the effectiveness of MSC-like human brain vascular pericytes [3] in a rat model of SCI. Excitingly, the study shows that these central nervous system-derived cells have a greater immunomodulatory potential than non-central nervous system tissue-derived cells, and so may be an effective new treatment for human SCI [4].

Throughout the study, the authors compared human brain vascular pericytes with another MSC cell type (umbilical cord matrix cells [HUCMCs]) with a similar marker expression profile. Intravenous delivery of both cell types at one day after SCI led to a significant accumulation of cells in the lungs, liver, and spleen although a small proportion of cells did reach the spinal cord. However, MSCs persisted in the spleen for up to 7 days and correlated to significantly increased splenic and circulating levels of the potent anti-inflammatory cytokine interleukin-10 (IL-10) and other more subtle changes to immunomodulatory factors. Together, this suggests that both MSC types may have a potent immunomodulatory effect.

Excitingly, administration of both cell types also reduced blood-spinal cord barrier (BSCB) permeability, the amount of hemorrhaging in the spinal cord, and the overall acute lesion volume at early time points. Furthermore, the study observed improved functional vascularity at the injury site, although there were no observed changes in blood vessel density. Lastly, and perhaps most encouragingly, MSC administration also induced functional recovery (forelimb motor function and whole-body limb function and trunk stability) and reduced lesional tissue and increased white matter sparing at 10 weeks (See figure). Interestingly, human brain vascular pericyte-treated animals uniquely improved whole body limb coordination and trunk stability, suggesting that they may be a better choice for SCI-treatment.

Through this first assessment of human brain vascular pericytes for SCI, we have the promise of a minimally invasive new treatment which can reduce secondary vascular pathology and promote recovery following SCI seemingly through a potent immunomodulatory effect. The authors hope that this study will also promote “further study of the splenic role in secondary pathology and cell based reparative mechanisms for future clinical translation” and will bring an effective new treatment to human patients in the near future.

References

  1. De Miguel MP, Fuentes-Julian S, Blazquez-Martinez A, et al. Immunosuppressive properties of mesenchymal stem cells: advances and applications. Curr Mol Med 2012;12:574-591.
  2. Alexanian AR, Kwok WM, Pravdic D, et al. Survival of neurally induced mesenchymal cells may determine degree of motor recovery in injured spinal cord rats. Restor Neurol Neurosci 2010;28:761-767.
  3. Williams K, Alvarez X, and Lackner AA Central nervous system perivascular cells are immunoregulatory cells that connect the CNS with the peripheral immune system. Glia 2001;36:156-164.
  4. Badner A, Vawda R, Laliberte A, et al. Early Intravenous Delivery of Human Brain Stromal Cells Modulates Systemic Inflammation and Leads to Vasoprotection in Traumatic Spinal Cord Injury. Stem Cells Transl Med 2016;5:991-1003.