Autologous cell using for the restoration of functional defects in patients with ischemic cerebrovascular accident

Abstract

Stroke is a global medical and socio-economic problem and a great demand for alternative therapies, the leading one being stem cell (SC) therapy. Pathogenetic processes in ischemic stroke (II) trigger the mechanisms of necrotic and apoptotic death of neurons with the formation of the central infarct zone («core of ischemia») and the ischemic «penumbra» zone; the severity and reversibility of the injury directly depends on the duration of ischemia. In parallel with pathogenetic processes, endogenous neurogenesis occurs – the proliferation of neurogenic stem and progenitor cells (NSC/NPC) and their migration into the ischemic focus; however, most NSCs and newly formed neurons undergo apoptosis and recovery of lost functions does not occur. Significant efforts are being made to find ways to control neurogenesis, in particular through the transplantation of exogenous SCs. The main factors preventing the use of SCs in humans are moral, ethical, religious and legal aspects related to the source and method of obtaining cells, as well as possible immunocompromised complications due to incompatibility of donor cells with the recipient of the main histocompatibility complex antigens. The safest is the use of autologous SCs (the patient’s own cells), as it does not require the use of immunosuppressive protocols. Due to the relative safety and ease of production, the most common are multipotent mesenchymal stem cells (MSCs), namely MSCs of the bone marrow (BM). Numerous preclinical studies in experimental animals with modeled II, as well as clinical trials conducted over the past 15 years, have shown the safety and feasibility of transplantation of autologous MSCs in patients with severe neurological deficits after II. Two different approaches to the use of MSCs are discussed: neuroprotection in the acute phase and neurorestoration in the chronic phase II. Proposals are currently being developed for phase II/III clinical trials in acute and chronic stroke using BM MSCs, the results of which will form the basis for certified standardized II treatment protocols.

The effect of mesenchymal stromal cells of various origins on morphology of hippocampal CA1 area of rats with acute cerebral ischemia

“…Various authors have shown that transplantation of MSCs after ischemic stroke improves brain function, effectively protects ischemic neurons and restores brain injury [12][13][14][15]. This is due to the fact that MSCs secrete a numerous trophic and immunomodulatory cytokines, commonly referred to as the MSC secretome, which has significant potential for the treatment of various diseases and brain injury through the induction of endogenous neuroprotection, neurogenesis, and angiogenesis [23,24].…”

“…To date, bone marrow-derived MSCs are the most studied and best characterized MSCs [12]. At the same time, even in recent studies, the main source of MSCs was bone marrow and adipose tissue, and only one study was performed with placental cells [13]. At the same time, as in our case, both allogeneic [14] and xenogeneic [15] cells were used in the research.…”

“…To analyze the effect of MSCs of various origin, lysate of human Wharton's jelly-derived MSCs and citicoline on the dynamics of destructive changes in the hippocampal CA1 area in 7 days (subacute ischemia) and 14 days (recovery period) after IR, rats were euthanized by decapitation with a previous overdose of pentobarbital (Bioveta JSC, Czech Republic) at the dose of 100 mg/kg [13,14,22].…”

Restoration of the nervous system in acute ischemia-reperfusion of the rat brain by intravenous administration of mesenchymal stromal cells of different origin

“…[23][24][25][26] To analyze the effects of MSCs of different origin, MSC lysate of human Wharton jelly cells and citicoline on the somatosensory area of the cortex and the CA1 zone of the hippocampus, the brains of rats were quickly removed after decapitation using pentobarbital anesthesia (Penbital, Bioveta a.s., Czech Republic, 100mg/ kg) after 7 days (subacute period of ischemia) and 14 days (recovery period) after IR. 15,27,28…”

“…6 Cell therapy using mesenchymal stromal cells (MSCs) demonstrated encouraging results regarding endogenous mechanisms of neuroregeneration in response to ischemic damage of brain structures. [9][10][11][12][13][14] The main source of MSCs is bone marrow, 15 however, due to age-related degeneration and the risk of infection, allogeneic umbilical cord Wharton's jelly MSCs are more accessible for obtaining and safer for humans. Such MSCs can be received in large amount, they are multipotent, proliferative, hypoimmunogenic, do not induce oncogenesis and are able to exist for a long time in the host's brain.…”