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Younger Stem Cells Enhance Functional Recovery from Spinal Cord Injury

Review of “Early Intravenous Infusion of Mesenchymal Stromal Cells Exerts a Tissue Source Age‐Dependent Beneficial Effect on Neurovascular Integrity and Neurobehavioral Recovery After Traumatic Cervical Spinal Cord Injury” from STEM CELLS Translational Medicine by Stuart P. Atkinson 

Previous studies from the laboratory of Michael G. Fehlings (University of Toronto, Ontario, Canada) demonstrated the effectiveness of the early infusion of mesenchymal stem (MSC)-like perivascular cells derived from the fetal brain in a rat model of spinal cord injury as an acute cell therapy that targets vascular disruption. The authors hoped that this could mitigate subsequent secondary vascular pathology and boost functional recovery and tissue preservation in the long term [1] (Read more in STEM CELLS Translational Medicine!). 

As fetal and embryonic cells generally exhibit greater proliferative potential in vitro and enhanced post-implantation survival, migration, and central nervous system integration, the authors have now compared term birth (HUCPVCs) and first‐trimester umbilical cord perivascular cells (FTM-HUCPVCs) [2] to adult bone marrow MSCs with regards to their longer-term functional recovery following early infusion in a clinically relevant rat model of spinal cord injury.

Encouragingly, Vawda et al. now report in STEM CELLS Translational Medicine on the similarities and differences between the therapeutic efficacies of the differently aged stem cells and establish that early intravenous HUCPVC infusion following spinal cord injury can foster long‐term improvements in multiple tissue and functional readouts [3]. 

Is younger better for functional recovery from spinal cord injury?

The authors employed a moderately severe cervical clip compression/contusion injury at the cervicothoracic junction in adult female rats followed shortly after by the minimally invasive intravenous administration of the distinct types of stem cells. While HUCPVC and FTM-HUCPVC treatment improved forelimb function when compared to a vehicle-only control, only the FTM-HUCPVC-treated rats displayed a significant gain in weight, thereby indicating enhanced long‐term functional recovery. 

Overall, this suggests that “younger” stem cells exhibit a therapeutic advantage over their “older” counterparts, perhaps due to the previously reported expression of stem/progenitor cell-associated genes [2] and enhanced angiogenic potency [4].

Subsequent immunohistochemical and ultrasound imaging analyses revealed that stem cell treatment reduced glial scarring and increased axonal, myelin, and vascular densities. Additionally, the authors employed an innovative ultrasound technology to accurately measure acute lesional volume in live animals [5], and while they noted a trend towards a reduce post‐traumatic cavity volume following stem cells treatment, this failed to reach a significant level. 

Of note, analysis of cell distribution established that systemically infused stem cells distributed mainly to the lung and spleen and not the lesional and peri‐lesional areas, suggesting that infused stem cells may serve as cellular decoys for the immune system or they may release anti‐inflammatory cytokines to influence immune cell recruitment and phenotype.

The authors of this encouraging study hope to carry out more detailed immunohistochemical analyses, study additional cell administration approaches, delineate which cells and what mechanisms provide the therapeutic output, the potential for stem cell priming, and explore clinically suitable culture conditions to enhance translation to the clinic. 

To discover just how younger stem cells can enhance functional recovery from spinal cord injury, stay tuned to the Stem Cells Portal!

References

  1. 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 Translational Medicine 2016;5:991-1003.
  2. Hong S-H, Maghen L, Kenigsberg S, et al., Ontogeny of Human Umbilical Cord Perivascular Cells: Molecular and Fate Potential Changes During Gestation. Stem Cells and Development 2013;22:2425-2439.
  3. Vawda R, Badner A, Hong J, et al., Early Intravenous Infusion of Mesenchymal Stromal Cells Exerts a Tissue Source Age-Dependent Beneficial Effect on Neurovascular Integrity and Neurobehavioral Recovery After Traumatic Cervical Spinal Cord Injury. STEM CELLS Translational Medicine 2019;8:639-649.
  4. Iqbal F, Szaraz P, Librach M, et al., Angiogenic potency evaluation of cell therapy candidates by a novel application of the in vitro aortic ring assay. Stem Cell Research & Therapy 2017;8:184.
  5. Soubeyrand M, Badner A, Vawda R, et al., Very High Resolution Ultrasound Imaging for Real-Time Quantitative Visualization of Vascular Disruption after Spinal Cord Injury. Journal of Neurotrauma 2014;31:1767-1775.