Abstract
In subacute and chronic phases of the stroke, there are no therapeutics available at present to promote functional recovery. Human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) are one of the candidate cell types for treating subacute-phase stroke. The benefits of cell-based therapy largely depend on the migratory capacity of products administered, as well as their potential for engraftment in targeted tissues and paracrine activities. Timing and delivery modes may also influence the outcomes of stem-cell therapy. Still, the functional recuperative effects of differing hUC-MSC delivery modes, about cell replacement and cell-to-cell paracrine activity levels, have yet to be clarified in subacute phases of stroke.This study was conducted to compare the therapeutic effects of various delivery routes when administering Good Manufacturing Practice (GMP)-grade hUC-MSCs in a rodent model of subacute-phase stroke. Cell aliquots (1 × 106) were given to rats as intravenous (IV) injections or intracerebral (IC) transplants 1 week after middle cerebral artery occlusion (MCAo). Transplanted rats were examined up to 7 weeks later using various behavioral tests and immunohistochemical analyses. Most IC-transplanted cells survived for short periods (i.e., <4 weeks after receipt) and gradually disappeared, whereas IV-injected cells were undetectable in the brain at the same time points (i.e., 3 days, 4 weeks, or 7 weeks after injection). Although short-lived, IC-transplanted cells effectively improved behavioral deficits, serving to reduce infarct volumes and glial scar formation, increase subventricular counts of proliferating neuroblasts, and promote cerebrovascular ingrowth in ischemic penumbra regions. IV injection, however, failed to improve behavioral function or histologic parameters during the same 7-week time frame. These findings overall suggest that IC transplantation is preferable to IV injection for delivery of hUC-MSCs during subacute phases of stroke.
Highlights
Severe brain damage inflicted by strokes leads to long-term disability or even death, and the need for more effective therapies is dire
They secrete multiple trophic factors for endogenous brain repair [vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF); Ranganath et al, 2012] and strong immune-modulating anti-inflammatory mediators [transforming growth factor-β (TGF-β), interleukin (IL)-10, and indoleamine 2,3-dioxygenase (IDO); Ranganath et al, 2012]; and they are present in abundance, found in bone marrow (Pittenger et al, 1999), adipose tissue (Zuk et al, 2002), umbilical cord (Erices et al, 2000), peripheral blood (Ukai et al, 2007), and dental pulp (Gronthos et al, 2000), as well as a wide range of mesodermal reservoirs that include perivascular sites in the brain (Kang et al, 2010; Paul et al, 2012)
Because the therapeutic window for thrombolytic therapy is quite narrow in clinical situations,
Summary
Severe brain damage inflicted by strokes leads to long-term disability or even death, and the need for more effective therapies is dire. The outcomes of IC transplantation seem to surpass those of IV injection in terms of functional recovery (Chrostek et al, 2019) Another issue for cell therapy is the timing of cell delivery. Because the therapeutic window for thrombolytic therapy is quite narrow in clinical situations,
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
