Induction of pluripotent stem cells transplantation therapy for ischemic stroke

Abstract

Stroke can cause permanent neurological damage, complications, and even death. However, there is no treatment exists to restore its lost function. Human embryonic stems transplantation therapy was a novel and potential therapeutic approach for stroke. However, as we have seen, the ethical controversy pertains to embryonic stem cell research. Human induced pluripotent stem cells (iPSCs) are the latest generation of stem cells that may be a solution to the controversy of using embryonic cells. In our study, we generated iPSCs from adult human fibroblasts by introduction of four defined transcription factors (Oct4, Sox2, Nanog, and Lin-28). And then, we investigated the efficacy of iPSCs transplantation therapy for stroke on the animal models of middle cerebral artery occlusion. Surprisingly, we found that transplanted iPSCs migrated to injured brain areas, and differentiated into neuron-like cells successfully. After 4-16 days iPSCs grafting, sensorimotor function of rats has been improved significantly. In one word, we may prove that iPSCs therapy in stroke to be an effective form of treatment.

Human-Induced Pluripotent Stem Cells form Functional Neurons and Improve Recovery After Grafting in Stroke-Damaged Brain

“…The studies with human iPSCs in stroke published so far provided no evidence for the formation of neuroblasts or morphologically mature neurons [25,26]. We found that at 4 months after human iPSC-derived lt-NES cells had been implanted into the striatum or cerebral cortex of Tcell-deficient rats in two different models of stroke, 73% and 77%, respectively, of grafted cells expressed the mature neuronal marker NeuN.…”

“…In support of this interpretation, the enhancement of behavioral recovery in our experiment was observed irrespective of whether the grafts were surviving at 10 weeks or not. Similarly, human iPSCs improved performance in the cylinder test from 4 days after intrastriatal implantation into stroke-damaged rats [25].…”

“…stroke, there was a reduction of the infarct volume and some behavioral improvement [24]. Finally, human fibroblastderived iPSCs implanted into the striatum of stroke-damaged rats were found to improve short-term sensorimotor recovery, but whether any neurons were formed is unclear [25]. Another recent study did not detect any effect of iPSCs on strokeinduced behavioral impairments at 4 weeks after transplantation [26].…”

Advances in the Combined Use of Adult Cell Therapy and Scaffolds for Brain Tissue Engineering

“…In the context of ischemic stroke, an interesting study describes the use of iPS-derived neurons and astrocytes directly injected in the damaged cortex of a stroke animal model , which resulted in a reduced ischemic size with functional improvements. Another study describes the in situ migration and differentiation of human iPS cells in a similar context, with an improved sensorimotor function of the animals 4-16 days after grafting (Jiang et al 2011). …”

Repair and regeneration properties of Ginkgo biloba after ischemic brain injury

“…Replacement of damaged tissue with cell-grafts or pluripotent stem cells that could differentiate into neural and glial cell populations has been widely studied (Modo et al, 2002; Jiang et al, 2011). In light of the practical and ethical issues restraining the field of stem cell research, alternative modes of stimulating neurogenesis are highly sought after.…”