Intravenous autologous bone marrow mononuclear cells for ischemic stroke

Savitz, Sean I; Misra, Vivek; Kasam, Mallikarjunarao; Juneja, Harrinder; Cox, Charles S.; Alderman, Susan; Aisiku, Imo; Kar, Siddhartha; Gee, Adrian P.; Grotta, James C.

doi:10.1002/ana.22458

Cited by 266 publications

(232 citation statements)

References 23 publications

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“…26 Ten small clinical studies of intravenous or intra-arterial cell delivery, including 136 subjects, have reported findings. [27][28][29][30][31][32][33][34][35][36] The majority of these were small, single-institution safety and tolerability studies. Only three included a control group, and the value of the control groups is questionable, since in many cases they consisted of patients deemed ineligible for the cell therapy intervention, were not randomised, and did not necessarily undergo any study related procedures.…”

Section: The Acute or Early Subacute Paradigmmentioning

confidence: 99%

Clinical trial design for stem cell therapies in stroke: What have we learned?

Muir

2017

Neurochemistry International

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Stem cells of various sources have been investigated in a series of small, safety and feasibility-focused studies over the past 15 years. Understanding of mechanisms of action has evolved and the trial paradigms have become focused on two different approaches -one being an early subacute delivery of cells to reduce acute tissue injury and modify the tissue environment in a direction favourable to reparative processes (for example by being anti-inflammatory, antiapoptotic, and encouraging endogenous stem cell mobilisation); the other exploring later delivery of cells during the recovery phase after stroke to modulate the local environment in favour of angiogenesis and neurogenesis. The former approach has generally investigated intravenous or intra-arterial delivery of cells with an expected paracrine mode of action and no expected engraftment within the brain. The latter has explored direct intracerebral implantation adjacent to the infarct. Several relevant trials have been conducted, including two controlled trials of intravenously delivered bone marrow-derived cells in the early subacute stage, and two small singlearm phase 1 trials of intracerebrally implanted cells. The findings of these studies and their implications for future trial design are considered.Introduction:

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Section: The Acute or Early Subacute Paradigmmentioning

confidence: 99%

Clinical trial design for stem cell therapies in stroke: What have we learned?

Muir

2017

Neurochemistry International

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“…The second one was performed using human neuronal cells and report the safety and feasibility of neuron transplantation for patients with motor stroke [35]. Other clinical trials using bone marrow derived stem cell (BMSC) in stroke have shown the feasibility and safety of the approach [36][37][38][39]. Moniche et al showed that the BMSC in subacute Middle Cerebral Artery (MCA) stroke patients could induce changes in serum levels of GranulocyteMacrophage Colony-Stimulating Factor (GM-CSF), platelet-derived growth factor-BB (PDGF-BB), and matrix metalloproteinases 2 (MMP-2), which could induce an improved functional outcomes [40].…”

Section: Neural Progenitor Cell Therapy In the Post-acute Phase Of Stmentioning

confidence: 99%

Current Stage and Future Perspective of Stem Cell Therapy in Ischemic Stroke

Ana-Maria¹,

Carmen²,

Tudorică³

2017

J Stem Cell Res Ther

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“…The direct intracerebral implantation of stem cells to the peri-infarct region is utilized for the chronic phase with the stroke brain more tolerant of an invasive treatment procedure, but also because of tapered levels of chemoattractants [62]. Direct transplantation was initially examined in chronic stroke patients using neural progenitor cells (NT2N) [63] and in recent years using Notch-induced bone marrow cells (SB-623) [64], with subsequent clinical trials employing intravenous and intra-arterial administration of MSCs in subacute stroke patients [65,66].…”

Section: Mscs Their Mechanism Of Action and Safety Profilementioning

confidence: 99%

“…Recent clinical trials on transplantation of MSCs have shown their safety in stroke [75,[79][80][81]. In addition to the small number of patients enrolled in these clinical trials, the translation of laboratory protocols for clinical transplant regimens has been marred with major discrepancies including the lack of well-defined release criteria of the donor cells, varying timing, cell dose and route of transplant intervention, altogether deviating from the established preclinical readouts.…”

Section: Translational Challenges Of Msc Therapy For Strokementioning

confidence: 99%

Mesenchymal stem cell-based therapy for ischemic stroke

et al. 2016

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Ischemic stroke represents a major, worldwide health burden with increasing incidence. Patients affected by ischemic strokes currently have few clinically approved treatment options available. Most currently approved treatments for ischemic stroke have narrow therapeutic windows, severely limiting the number of patients able to be treated. Mesenchymal stem cells represent a promising novel treatment for ischemic stroke. Numerous studies have demonstrated that mesenchymal stem cells functionally improve outcomes in rodent models of ischemic stroke. Recent studies have also shown that exosomes secreted by mesenchymal stem cells mediate much of this effect. In the present review, we summarize the current literature on the use of mesenchymal stem cells to treat ischemic stroke. Further studies investigating the mechanisms underlying mesenchymal stem cells tissue healing effects are warranted and would be of benefit to the field.

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Intravenous autologous bone marrow mononuclear cells for ischemic stroke

Abstract: This study suggests that a bone marrow harvest and reinfusion of autologous MNCs were safe and feasible in acute stroke patients.

Cited by 266 publications

References 23 publications

Clinical trial design for stem cell therapies in stroke: What have we learned?

Clinical trial design for stem cell therapies in stroke: What have we learned?

Current Stage and Future Perspective of Stem Cell Therapy in Ischemic Stroke

Mesenchymal stem cell-based therapy for ischemic stroke

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