Intrathecal Transplantation of Autologous and Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells in Dogs

Benavides, Felipe Pérez; Pinto, Giovana Boff Araujo; Heckler, Marta Cristina Thomas; Hurtado, Diana Milena Rodríguez; Teixeira, L. R.; Monobe, Marina Mitie de Souza; Machado, Gisele Fabrino; Melo, Guilherme Dias de; Rodríguez-Sánchez, Diego Noé; Alvarenga, Fernanda da Cruz Landim e; Amorim, Rogério Martins

doi:10.1177/09636897211034464

Cited by 10 publications

(8 citation statements)

References 61 publications

(86 reference statements)

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“…Recent clinical and preclinical studies have established the safety of intrathecal MSC transplantation. Intrathecal infusion of 1.5 × 10 6 BM-MSCs in dogs did not produce any differences in the number of nucleated cells or the levels of pro-MMP2 or MMP9 in the CSF before or after transplantation and MRI analysis one year post-transplantation did not reveal alterations in the brain [ 25 ]. Similarly, intrathecal infusion of 1.0 × 10 6 BM-MSCs in horses did not produce changes in CSF cell count or pro-MMP2 level or cause signs of the neurological disorder [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…The rate of CSF secretion equals that of its removal, so obstruction of flow allows fluid accumulation and causes enlargement of the cavity in front of the blockage. Although several studies have demonstrated the feasibility of intrathecal transplantation of MSCs, the influence on CSF flow has not been carefully examined [ 22 , 24 , 25 ]. MSCs are known for their tendency to self-assemble and spontaneously form aggregates in suspensions [ 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Mesenchymal stem cell aggregation mediated by integrin α4/VCAM-1 after intrathecal transplantation in MCAO rats

Dong

et al. 2022

Stem Cell Res Ther

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Background Mesenchymal stem cells (MSCs) have shown immense therapeutic potential for various brain diseases. Intrathecal administration of MSCs may enhance their recruitment to lesions in the central nervous system, but any impact on cerebrospinal fluid (CSF) flow remains unclear. Methods Rats with or without middle cerebral artery occlusion (MCAO) received intrathecal injections of 2D cultured MSCs, 3D cultured MSCs or an equal volume of artificial cerebrospinal fluid (ACSF). Ventricle volume was assessed by MRI on Days 2 and 14 post-MCAO surgery. A beam walking test was used to assess fine motor coordination and balance. Aggregation of MSCs was evaluated in CSF and frozen brain tissue. Differential expression of cell adhesion molecules was evaluated by RNA-Seq, flow cytometry and immunofluorescence analyses. The influence of VCAM-1 blockade in mediating the aggregation of 2D MSCs was investigated in vitro by counting cells that passed through a strainer and in vivo by evaluating ventricular dilation. Results MSC expanded in 2D culture formed aggregates in the CSF and caused ventricular enlargement in both MCAO and normal rats. Aggregates were associated with impaired motor function. 2D MSCs expressed higher levels of integrin α4 and VCAM-1 than 3D MSCs. Blockade of VCAM-1 in 2D MSCs reduced their aggregation in vitro and reduced lateral ventricular enlargement after intrathecal infusion. 3D MSCs exhibited lower cell aggregation and reduced cerebral ventricular dilation after intrathecal transplantation Conclusions The aggregation of 2D MSCs, mediated by the interaction of integrin α4 and VCAM-1, is a potential risk for obstruction of CSF flow after intrathecal transplantation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell aggregation mediated by integrin α4/VCAM-1 after intrathecal transplantation in MCAO rats

Dong

et al. 2022

Stem Cell Res Ther

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“…For clinical strategies, the main concept is the morphological and functional reestablishment of bone tissue. Current therapeutic treatments for bone tissues include bone transplantation (e.g., autogenous bone or allogeneic bone), (Behrend et al, 2016), bone substitution materials (e.g., titanium plate), (Diwu et al, 2020), stem cell transplantation (e.g., bone marrow stem cells, bMSCs), (Benavides et al, 2021), biological agents (e.g., growth factors), (Kitaura et al, 2022), gene therapy, (Gao et al, 2022), distraction osteogenesis, (Qi et al, 2009), and barrier membrane to guide bone regeneration. (Han et al, 2018) The purposes of applying bone filling materials in guided bone regeneration (GBR) procedures are: 1) supporting the barrier film to avoid collapse; (Cox et al, 2022) 2) scaffolding for new bone to grow in from the receptive area; (Roseti et al, 2017) 3) stimulating the growth of new bone from the receptive area; (Robling and Bonewald, 2020) 4) resisting to surface soft tissue pressure; (Hao et al, 2022) 5) protecting the new bone mass and avoiding its absorption.…”

Section: Introductionmentioning

confidence: 99%

The biological applications of exosomal-based materials in bone/cartilage tissue engineering

Chen

Cheng²,

Zhang³

et al. 2023

Front. Mater.

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Exosomes are secreted by various cells including stem cells, dendritic cells, and tumor cells, also known as the cell-derived extracellular vesicles. Exosomes, can carry informative cargos from host cells, thus have been employed as potential nanomaterials for their multifarious biological functions in biomedical fields, such as drug and genes delivery, tumor targeting, and disease treatment. Recently, the biological applications of exosomes in bone tissue engineering have gained increasing attention. Some important progress has been made while the tissue regeneration and functional recovery of boneremain as the key challenges to be addressed. In this article, we first made a summary of exosomes and their applications in the regeneration of bone and cartilage tissue. Then, modification approaches used for exosomes to equip them with excellent capacities are summarized. Finally, current concerns and future outlooks of exosomes in bone/cartilage tissue engineering and regeneration are discussed.

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“…Regardless of route of administration, in nearly all published studies, allogeneic MSCs (alloMSCs) were used, requiring concomitant treatment with harsh immunosuppressant drugs to prevent the rapid immunorejection of transplanted cells [48,49]. Except for several rodent studies [35,40,50], there remains scant information on the potential utility of autologous MSCs (autoMSCs) which lack immunogenicity. The ability of autoor alloMSCs to improve recovery in chronic stroke models remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Intracerebral Transplantation of Autologous Mesenchymal Stem Cells Improves Functional Recovery in a Rat Model of Chronic Ischemic Stroke

Myers

Hines

Gray

et al. 2023

Preprint

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While treatments exist for the acute phase of stroke, there are limited options for patients with chronic infarcts and long-term disability. Allogenic mesenchymal stem cells (alloMSCs) show promise for the treatment of stroke soon after ischemic injury. There is, however, no information on the use of a) autologous MSCs (autoMSCs), b) delivered via intracerebral transplantation c) in rats with a chronic infarct. In this study, rats underwent middle cerebral artery occlusion (MCAO) to induce stroke followed by bone marrow aspiration and MSC expansion in a closed bioreactor. Four weeks later, brain MRI was obtained and autoMSCs (1x106, 2.5x106 or 5x106; n = 6 each) were stereotactically injected into the peri-infarct and compared to controls (MCAO only; MCAO + PBS; n = 6–9). Behavior was assessed using the modified neurological severity score (mNSS). For comparison, an additional cohort of MCAO rats were implanted with 2.5x106 alloMSCs generated from a healthy rat. At all doses of autoMSCs, sensorimotor function significantly improved by over 64% 60 days later while alloMSCs improved only 29.2%, similar to that in PBS control animals. Quantum dot labeled auto/alloMSCs were found exclusively at the implantation site throughout the post-transplantation period with no tumor formation on MRI or Ki67 staining in engrafted MSCs. Small differences in stroke volume and no differences in corpus callosum width were observed after MSC treatment. Stroke-induced glial reactivity in the peri-infarct was long-lasting and unabated by auto/alloMSC transplantation. These studies suggest that intracerebral transplantation of autoMSCs, but not alloMSCs, may be a more promising treatment in chronic stroke.

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Intrathecal Transplantation of Autologous and Allogeneic Bone Marrow-Derived Mesenchymal Stem Cells in Dogs

Cited by 10 publications

References 61 publications

Mesenchymal stem cell aggregation mediated by integrin α4/VCAM-1 after intrathecal transplantation in MCAO rats

Mesenchymal stem cell aggregation mediated by integrin α4/VCAM-1 after intrathecal transplantation in MCAO rats

The biological applications of exosomal-based materials in bone/cartilage tissue engineering

Intracerebral Transplantation of Autologous Mesenchymal Stem Cells Improves Functional Recovery in a Rat Model of Chronic Ischemic Stroke

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