Changes in Host Blood Factors and Brain Glia Accompanying the Functional Recovery after Systemic Administration of Bone Marrow Stem Cells in Ischemic Stroke Rats

Yang, Ming; Wei, Xiaotao; Li, Jing; Heine, L; Rosenwasser, Robert H.; Iacovitti, Lorraine

doi:10.3727/096368910x503415

Cited by 82 publications

(91 citation statements)

References 62 publications

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“…24 This, in turn, may be mediated by the outgrowth of nerve fibers of endogenous neurons. 23,25 Other studies have demonstrated that stem cell therapy results in the upregulation of growth factors that may be responsible for the outgrowth of these endogenous fiber processes 26 and for the inhibition of inflammatory processes, 27 which may lead to secondary cell loss within the brain. These observations offer intriguing alternative mechanisms that may underlie the restorative effects noted with stem cell therapy following stroke and provide a rationale basis for clinical trials.…”

Section: Mechanisms Of Action Of Stem Cells In Ischemic Strokementioning

confidence: 99%

Stem cell therapy in ischemic stroke

et al. 2012

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Objective: Cell-based therapies are being investigated as an adjunct to IV thrombolysis or mechanical thrombectomy in ischemic stroke. This review summarizes the potential applications as well as challenges of intravascular cell delivery in ischemic stroke. Method:We conducted a search of Medline as well as the clinicaltrials.gov Web site for all ongoing human clinical studies using stem cells in ischemic stroke patients. Result:The pros and cons of the various donor cell types and routes of cell delivery, including intravascular delivery, in ischemic stroke are discussed. In addition, the potential challenges in translation from bench to bedside, the optimal techniques for intravascular cell delivery, and an updated comprehensive list of ongoing clinical trials in ischemic stroke are highlighted. Conclusions:Stem cells have shown a promising role in ischemic stroke, in preclinical studies as well as initial pilot studies. Further studies are needed to assess intravascular cell therapy as a potential adjunct to thrombolysis or mechanical thrombectomy in ischemic stroke. Neurology Cell therapy is emerging as a promising new modality for enhancing neurologic recovery in ischemic stroke.1 Numerous basic science studies have demonstrated positive results in animal models of ischemic stroke following implantation of progenitor cells derived from various sources, including adipose, human fetal/embryonic tissue, bone marrow, peripheral, and umbilical cord blood (figure).2 These animal studies have utilized various methods of cell delivery or implantation (table 1), including direct intracerebral (IC) injection, intracisternal/cerebroventricular (ICV), or intravascular routes of delivery such as IV or intra-arterial (IA) infusion.Methods of cellular delivery and implantation. Intracerebral. Direct injection is invasive, and despite being a precise method of cellular delivery and implantation, it results in a poor distribution of cells in the target lesion.3 Initial pilot human studies investigating stereotactic IC cell implantation in patients with chronic stroke also reported adverse events, including seizures, syncope, asymptomatic subdural hematoma, transient motor worsening, and enhancing lesions on MRI. 4,5Intracisternal/cerebroventricular. The ICV route of cell delivery is less invasive than direct IC implantation but is also associated with variable cell migration to the ischemic site.6,7 In a pilot human study investigating ICV delivery in 10 chronic stroke patients (7 ischemic and 3 hemorrhagic), some patients developed fever and meningeal signs 48 hours after cellular delivery via ICV route. IV.Infusion is the least invasive method, allowing wide distribution of cells with exposure to chemotactic signals that potentially guide them toward the target ischemic lesion. This method, however, results in cells being trapped by peripheral organs, including the lungs, liver, and spleen, thereby limiting potential engraftment in the ischemic lesion in the brain.2 Since patients with ischemic stroke commonly ha...

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Section: Mechanisms Of Action Of Stem Cells In Ischemic Strokementioning

confidence: 99%

Stem cell therapy in ischemic stroke

et al. 2012

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“…A major component of regenerative medicine is stem cell-based therapeutics, which have shown promising therapeutic potential for various types of neurological disorders, including TBI (e.g., 57,58,62,109,130), and have reached limited clinical trials [for review see (43)]. Translating cell therapy for treatment of brain diseases to the clinic has involved testing the safety, efficacy, and mechanisms of action of a variety of transplantable donor cells, including fetal stem cells, cancer-derived neuron-like cells, embryonic stem cells, induced pluripotent stem cells, and adult stem cells, such as umbilical cord blood, bone marrow stromal cells, amnion cells, among others (16,57,58,62,63,74,75,84,87,90,109,130). However, among these various types of stem cells, adult stem cells are of interest, as they circumvent ethical and moral problems and also teratogenic and oncogenic risks usually associated with transplantation of embryonal or fetal-derived stem cells (85).…”

Section: Stem Cell Transplantation In Tbimentioning

confidence: 99%

G-CSF as an Adjunctive Therapy with Umbilical Cord Blood Cell Transplantation for Traumatic Brain Injury

et al. 2015

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Traumatic brain injury (TBI), a major contributor to deaths and permanent disability worldwide, has been recently described as a progressive cell death process rather than an acute event. TBI pathophysiology is complicated and can be distinguished by the initial primary injury and the subsequent secondary injury that ensues days after the trauma. Therapeutic opportunities for TBI remain very limited with patients subjected to surgery or rehabilitation therapy. The efficacy of stem cell-based interventions, as well as neuroprotective agents in other neurological disorders of which pathologies overlap with TBI, indicates their potential as alternative TBI treatments. Furthermore, their therapeutic limitations may be augmented when combination therapy is pursued instead of using a single agent. Indeed, we demonstrated remarkable combined efficacy of human umbilical cord blood (hUCB) cell therapy and granulocyte-colony-stimulating factor (G-CSF) treatment in TBI models, providing essential evidence for the translation of this approach to treat TBI. Further studies are warranted to determine the mechanisms underlying therapeutic benefits exerted by hUCB + G-CSF in order to enhance its safety and efficacy in the clinic.

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“…Most studies have administered cells early (6-48 h) or at subacute phase (2-7 days) after stroke and only few comparisons have been made. Omori et al (2008) compared multiple time points and found that the greatest functional benefit was achieved when BM-MSCs were injected 6 h after stroke compared to later time points, which is supported by the finding of Yang et al (2010) that cells delivered 1 day have greater effect than those at 7 days. Instead, Mays et al (2010) reported time window from 1 to 7 days post-stroke to be equally beneficial.…”

Section: Adult Stem/progenitor Cellsmentioning

confidence: 51%

“…When considering studies using human cells, mostly bone marrow stem/stromal cells (BM-MSC) (Li et al, 2002;Zhao et al, 2002;Chen et al, 2003;Zhang et al, 2004;Omori et al, 2008;Andrews et al, 2008;Mays et al, 2010;Yang et al, 2010;Bao et al, 2011) or UCBCs (Chen et al, 2001;Willing et al, 2003a;Borlongan et al, 2004;Vendrame et al, 2004;Xiao et al, 2005;Newcomb et al, 2006;Chen et al, 2006;Mäkinen et al, 2006;Zhang et al, 2011;Riegelsberger et al, 2011) have been used. Most studies have administered cells early (6-48 h) or at subacute phase (2-7 days) after stroke and only few comparisons have been made.…”

Section: Adult Stem/progenitor Cellsmentioning

confidence: 99%