Various Cell Populations Within the Mononuclear Fraction of Bone Marrow Contribute to the Beneficial Effects of Autologous Bone Marrow Cell Therapy in a Rodent Stroke Model

Yang, Bing; Parsha, Kaushik; Schaar, Krystal; Xi, Xiao Pei; Aronowski, Jaroslaw; Savitz, Sean I

doi:10.1007/s12975-016-0462-x

Cited by 27 publications

(20 citation statements)

References 27 publications

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“…Despite their promising results to improve structural recovery, complete functional improvement has still not been achieved [13-15]. Different from other types of cell therapies, therapy with BMMCs consists of a mixture of lymphoid, myeloid, erythroid, and stem cell populations, and specifically in humans, of T cells, B cells, monocytes, natural killer cells, and hematopoietic progenitor cells [16, 17]. However, BMMCs have the advantage of easy isolation and separation of adequate amounts of BMMCs from a bone marrow aspiration, providing benefits similar to those obtained with MSCs [18, 19].…”

Section: Introductionmentioning

confidence: 99%

Bone Marrow–Derived Mononuclear Cell Therapy Accelerates Renal Ischemia-Reperfusion Injury Recovery by Modulating Inflammatory, Antioxidant and Apoptotic Related Molecules

Ornellas¹,

Ornellas²,

Martini³

et al. 2017

Cell Physiol Biochem

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Background/Aims: We investigated the regenerative capacity of intravenous administration of bone marrow–derived mononuclear cells (BMMCs) in a rat model of bilateral renal ischemia/reperfusion (IR) injury and the involvement of inflammatory anti-inflammatory and other biological markers in this process. Methods: Rats were subjected to 1h bilateral renal pedicle clamping. BMMCs were injected i.v 1h after reperfusion and tracked by ^99mTc and GFP+ BMMCs. Twenty-four hours after reperfusion, renal function and histological changes were evaluated. The mRNA (real time PCR) and protein (ELISA and immuno-staining) expression of biological markers were analyzed. Results: Renal function and structure improved after infusion of BMMCs in the IR group (IR-C). Labeled BMMCs were found in the kidneys after therapy. The expression of inflammatory and biological markers (TLR-2, TRL-4, RAGE, IL-17, HMGB-1, KIM-1) were reduced and the expression of anti-inflammatory and antioxidant markers (IL-10, Nrf2, and HO-1) were increased in IR-C animals compared with IR untreated animals (IR-S). The apoptotic index diminished and the proliferation index increased in IR-C compared with IR-S. Conclusion: The results contribute to our understanding of the role of different biological players in morphofunctional renal improvement and cytoprotection in a post-ischemic reperfusion kidney injury model subjected to cellular therapy.

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Section: Introductionmentioning

confidence: 99%

Bone Marrow–Derived Mononuclear Cell Therapy Accelerates Renal Ischemia-Reperfusion Injury Recovery by Modulating Inflammatory, Antioxidant and Apoptotic Related Molecules

Ornellas¹,

Ornellas²,

Martini³

et al. 2017

Cell Physiol Biochem

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“…[5–6] Therefore, reducing the brain infiltration of peripheral immune cells and reducing cerebral inflammation after stroke may represent effective therapeutic strategies. [7]…”

Section: Introductionmentioning

confidence: 99%

DRα1-MOG-35-55 Reduces Permanent Ischemic Brain Injury

Wang

et al. 2016

Transl. Stroke Res.

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Stroke induces a catastrophic immune response that involves the global activation of peripheral leukocytes, especially T cells. The HLA-DRα1 domain linked to MOG-35-55 peptide (DRα1-MOG-35-55) is a partial major histocompatibility complex II (MHC II) construct which can inhibit neuroantigen-specific T cells and block binding of the cytokine/chemokine macrophage migration inhibitory factor (MIF) to its CD74 receptor on monocytes and macrophages. Here, we evaluated the therapeutic effect of DRα1-MOG-35-55 in a mouse model of permanent distal middle cerebral artery occlusion (dMCAO). DRα1-MOG-35-55 was administered to WT C57BL/6 mice by subcutaneous injection starting 4h after the onset of ischemia followed by 3 daily injections. We demonstrated that DRα1-MOG-35-55 post-treatment significantly reduced brain infarct volume, improved functional outcomes and inhibited the accumulation of CD4+ and CD8+ T cells and expression of pro-inflammatory cytokines in the ischemic brain 96h after dMCAO. In addition, DRα1-MOG-35-55 treatment shifted microglia/macrophages in the ischemic brain to a beneficial M2 phenotype without changing their total numbers in the brain or blood. This study demonstrates for the first time the therapeutic efficacy of the DRα1-MOG-35-55 construct in dMCAO across MHC class II barriers in C57BL/6 mice. This MHC independent effect obviates the need for tissue typing and will thus greatly expedite treatment with DRα1-MOG-35-55 in human stroke subjects. Taken together, our findings suggest that DRα1-MOG-35-55 treatment may reduce ischemic brain injury by regulating post-stroke immune responses in the brain and the periphery.

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“…In addition, academic-industry collaborations are needed to overcome the translational stroke research roadblock, such as the advent of the multicenter preclinical trial concept [20]. Although the guidelines stem from the need to assess neuroprotection for acute ischemic stroke, they have been applied to the evaluation of other treatments, interventions, and fields of neuroscience with or without a modification [21][22][23][24][25][26].…”

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confidence: 99%