Preclinical progenitor cell therapy in traumatic brain injury: a meta-analysis

Jackson, Margaret L.; Srivastava, Amit K.; Cox, Charles S.

doi:10.1016/j.jss.2017.02.078

Cited by 19 publications

(12 citation statements)

References 71 publications

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“…MSCs are a similar cell type relative to MAPC, in that they are an adherent, bone-marrow-derived cell, but they differ in terms of ultimate product profile in terms of potency, size, and expansion characteristics. There are numerous publications that report the efficacy of MSCs in animal models of TBI, and this was reviewed in a meta-analysis of preclinical models of TBI using a cellular therapeutic (11). A reported mechanism of action is that cells migrate to the site of injury and exert a paracrine effect by secreting growth factors that preserve at risk neurons.…”

Section: Spinal Cord Injurymentioning

confidence: 99%

Cellular therapy for traumatic neurological injury

Cox

2017

Pediatr Res

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Neurological injury is the primary lethal mechanism of injury in children, and the primary etiology of long-term disability after trauma. Laboratories and clinical/translational teams have sought to develop stem/progenitor cell therapies to improve recovery in a clinical setting in which there is no significant reparative option. While none of these treatments are currently standard therapeutics, phase IIb clinical trials are underway in both adults and children in severe traumatic brain injury (TBI) and phase I/IIa trials in spinal cord injury. This review will characterize the cell therapy strategies: cell replacement and tissue integration vs. immunomodulation/enhanced endogenous tissue repair. TBI is somewhat different from other central nervous system injuries (spinal cord injury and stroke), in that TBI is a diffuse injury, whereas spinal cord injury and stroke are anatomically discrete. Importantly, this drives cell therapy approaches, as TBI is less apt to be treatable with a local cell replacement intervention. More localized injuries may be more amenable to local approaches and cell replacement to bridge focal gaps. This review focuses on a few reports in the field that highlight areas of progress, but is not intended to be a comprehensive survey of the state of regenerative medicine for neurological injuries.

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Section: Spinal Cord Injurymentioning

confidence: 99%

Cellular therapy for traumatic neurological injury

Cox

2017

Pediatr Res

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“…Microglia are the resident myeloid cells within the central nervous system (CNS) parenchyma and are key mediators of the neuroinflammatory response after TBI 3,8,9 . Our lab has investigated the use of cell therapies to attenuate the microglia‐mediated inflammatory response and have found that human mesenchymal stromal cells (MSC) and, recently, human cord blood‐derived regulatory T cell (Treg) therapy both decrease the neuroinflammatory response after TBI 6,10,11 . We believe that a primary mechanism by which cell therapies mitigate the inflammatory response is via interaction with the host immune system, specifically endogenous Treg 10,12 .…”

Section: Introductionmentioning

confidence: 99%

Combination therapy with Treg and mesenchymal stromal cells enhances potency and attenuation of inflammation after traumatic brain injury compared to monotherapy

et al. 2020

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The inflammatory response after traumatic brain injury (TBI) can lead to significant secondary brain injury and chronic inflammation within the central nervous system. Cell therapies, including mesenchymal stromal cells (MSC), have led to improvements in animal models of TBI and are under investigation in human trials. One potential mechanism for the therapeutic potential of MSC is their ability to augment the endogenous response of immune suppressive regulatory T cells (Treg). We have recently shown that infusion of human cord blood Treg decreased chronic microgliosis after TBI and altered the systemic immune response in a rodent model. These cells likely use both overlapping and distinct mechanisms to modulate the immune system; therefore, combining Treg and MSC as a combination therapy may confer therapeutic benefit over either monotherapy. However, investigation of Treg + MSC combination therapy in TBI is lacking. In this study, we compared the ability MSC + Treg combination therapy, as well as MSC and Treg monotherapies, to inhibit the neuroinflammatory response to TBI in vivo and in vitro. Treg + MSC combination therapy demonstrated increased potency to reduce the neuro- and peripheral inflammatory response compared to monotherapy; furthermore, the timing of infusion proved to be a significant variable in the efficacy of both MSC monotherapy and Treg + MSC combination therapy in vivo and in vitro.

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“…This study demonstrated a strong effect of cell therapy on reducing lesion volume, improving neurosensory (Rota‐Rod) and memory (Morris water maze) outcomes 122 . Preclinical data supports progenitor cell therapy for TBI 123‐125 …”

Section: Introductionmentioning

confidence: 52%

Progenitor cell therapy for acquired pediatric nervous system injury: Traumatic brain injury and acquired sensorineural hearing loss

Baumgartner

et al. 2020

Stem Cells Translational Medicine

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While cell therapies hold remarkable promise for replacing injured cells and repairing damaged tissues, cell replacement is not the only means by which these therapies can achieve therapeutic effect. For example, recent publications show that treatment with varieties of adult, multipotent stem cells can improve outcomes in patients with neurological conditions such as traumatic brain injury and hearing loss without directly replacing damaged or lost cells. As the immune system plays a central role in injury response and tissue repair, we here suggest that multipotent stem cell therapies achieve therapeutic effect by altering the immune response to injury, thereby limiting damage due to inflammation and possibly promoting repair. These findings argue for a broader understanding of the mechanisms by which cell therapies can benefit patients. K E Y W O R D S autologous stem cell transplantation, bone marrow, clinical translation, progenitor cells, umbilical cord blood 1 | INTRODUCTION This review will first consider two neurological conditions with unappreciated similarities: traumatic brain injury (TBI) and sensorineural hearing loss (SNHL), paying particular attention to the role of the immune system in each. Next, it will review laboratory and clinical findings showing improved outcomes for TBI and SNHL upon treatment with allogenic or autologous stem cells, including mesenchymal progenitor cells (MPCs)-a range of nonhematopoietic, mesodermal lineage, multipotent stem cells. 1 Finally, it will evaluate the possible mechanisms of action, concentrating on the immune modulatory properties of MPCs.

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Preclinical progenitor cell therapy in traumatic brain injury: a meta-analysis

Cited by 19 publications

References 71 publications

Cellular therapy for traumatic neurological injury

Cellular therapy for traumatic neurological injury

Combination therapy with Treg and mesenchymal stromal cells enhances potency and attenuation of inflammation after traumatic brain injury compared to monotherapy

Progenitor cell therapy for acquired pediatric nervous system injury: Traumatic brain injury and acquired sensorineural hearing loss

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