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

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Abstract

The route used in the transplantation of mesenchymal stem cells (MSCs) can directly affect the treatment success. The transplantation of MSCs via the intrathecal (IT) route can be an important therapeutic strategy for neurological disorders. The objective of this study was to evaluate the safety and feasibility of the IT transplantation of autologous (Auto-MSCs) and allogeneic (Allo-MSCs) bone marrow mesenchymal stem cells (BM-MSCs) in healthy dogs. Based on neurodisability score, cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI), no significant differences from the control group were observed on day 1 or day 5 after IT Auto- or Allo-MSCs transplantation ( P > 0.05). In addition, analysis of matrix metalloproteinase (MMP)-2 and MMP-9 expression in the CSF revealed no significant differences ( P > 0.05) at 5 days after IT transplantation in the Auto- or Allo-MSCs group when compared to the control. Intrathecal transplantation of BM-MSCs in dogs provides a safe, easy and minimally invasive route for the use of cell-based therapeutics in central nervous system diseases.

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Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.

M Dominici, K Le Blanc, I. Mueller … (2006)

The considerable therapeutic potential of human multipotent mesenchymal stromal cells (MSC) has generated markedly increasing interest in a wide variety of biomedical disciplines. However, investigators report studies of MSC using different methods of isolation and expansion, and different approaches to characterizing the cells. Thus it is increasingly difficult to compare and contrast study outcomes, which hinders progress in the field. To begin to address this issue, the Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy proposes minimal criteria to define human MSC. First, MSC must be plastic-adherent when maintained in standard culture conditions. Second, MSC must express CD105, CD73 and CD90, and lack expression of CD45, CD34, CD14 or CD11b, CD79alpha or CD19 and HLA-DR surface molecules. Third, MSC must differentiate to osteoblasts, adipocytes and chondroblasts in vitro. While these criteria will probably require modification as new knowledge unfolds, we believe this minimal set of standard criteria will foster a more uniform characterization of MSC and facilitate the exchange of data among investigators.

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Mesenchymal stem cells: immune evasive, not immune privileged.

James Ankrum, Joon Faii Ong, Jeffrey M Karp (2014)

The diverse immunomodulatory properties of mesenchymal stem/stromal cells (MSCs) may be exploited for treatment of a multitude of inflammatory conditions. MSCs have long been reported to be hypoimmunogenic or 'immune privileged'; this property is thought to enable MSC transplantation across major histocompatibility barriers and the creation of off-the-shelf therapies consisting of MSCs grown in culture. However, recent studies describing generation of antibodies against and immune rejection of allogeneic donor MSCs suggest that MSCs may not actually be immune privileged. Nevertheless, whether rejection of donor MSCs influences the efficacy of allogeneic MSC therapies is not known, and no definitive clinical advantage of autologous MSCs over allogeneic MSCs has been demonstrated to date. Although MSCs may exert therapeutic function through a brief 'hit and run' mechanism, protecting MSCs from immune detection and prolonging their persistence in vivo may improve clinical outcomes and prevent patient sensitization toward donor antigens.

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Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis.

Dimitrios Karussis, Clementine Karageorgiou, Adi Vaknin-Dembinsky … (2010)

To evaluate the feasibility, safety, and immunological effects of intrathecal and intravenous administration of autologous mesenchymal stem cells (MSCs) (also called mesenchymal stromal cells) in patients with multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). A phase 1/2 open-safety clinical trial. Patients Fifteen patients with MS (mean [SD] Expanded Disability Status Scale [EDSS] score, 6.7 [1.0]) and 19 with ALS (mean [SD] Amyotrophic Lateral Sclerosis Functional Rating Scale [ALSFRS] score, 20.8 [8.0]) were enrolled. Intervention After culture, a mean (SD) of 63.2 × 10(6) (2.5 × 10(6)) MSCs was injected intrathecally (n = 34) and intravenously (n = 14). In 9 cases, MSCs were magnetically labeled with the superparamagnetic iron oxide ferumoxides (Feridex). The main outcome measure was the recording of side effects. Follow-up (≤25 months) included adverse events evaluation, neurological disability assessment by means of the EDSS, magnetic resonance imaging to exclude unexpected pathologies and track the labeled stem cells, and immunological tests to assess the short-term immunomodulatory effects of MSC transplantation. Twenty-one patients had injection-related adverse effects consisting of transient fever, and 15 reported headache. No major adverse effects were reported during follow-up. The mean ALSFRS score remained stable during the first 6 months of observation, whereas the mean (SD) EDSS score improved from 6.7 (1.0) to 5.9 (1.6). Magnetic resonance imaging visualized the MSCs in the occipital horns of the ventricles, indicating the possible migration of ferumoxides-labeled cells in the meninges, subarachnoid space, and spinal cord. Immunological analysis revealed an increase in the proportion of CD4(+)CD25(+) regulatory T cells, a decrease in the proliferative responses of lymphocytes, and the expression of CD40(+), CD83(+), CD86(+), and HLA-DR on myeloid dendritic cells at 24 hours after MSC transplantation. Transplantation of MSCs in patients with MS and ALS is a clinically feasible and relatively safe procedure and induces immediate immunomodulatory effects. Trial Registration clinicaltrials.gov Identifier: NCT00781872.

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Author and article information

Journal

Journal ID (nlm-ta): Cell Transplant

Journal ID (iso-abbrev): Cell Transplant

Journal ID (publisher-id): CLL

Journal ID (hwp): spcll

Title: Cell Transplantation

Publisher: SAGE Publications (Sage CA: Los Angeles, CA )

ISSN (Print): 0963-6897

ISSN (Electronic): 1555-3892

Publication date (Electronic): 24 August 2021

Publication date Collection: Jan-Dec 2021

Volume: 30

Electronic Location Identifier: 09636897211034464

Affiliations

[1 ]Department of Veterinary Clinics, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), 18618-681-Botucatu, SP, Brazil

[2 ]Department of Animal Reproduction and Veterinary Radiology, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil

[3 ]Department of Veterinary Surgery and Anesthesiology, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil

[4 ]Department of Clinics, Surgery and Animal Reproduction, São Paulo State University (UNESP), Araçatuba, São Paulo, Brazil

Author notes

[*]Rogério Martins Amorim, Department of Veterinary Clinics, School of Veterinary Medicine and Animal Science, São Paulo State University (UNESP), Prof. Doutor Walter Mauricio Correia Street, UNESP, Campus de Botucatu, 18618-681-Botucatu, SP, Brazil. Email: rogerio.amorim@ 123456unesp.br

Author information

Guilherme Dias de Melo https://orcid.org/0000-0003-0747-7760

Diego Noé Rodríguez-Sánchez https://orcid.org/0000-0001-6524-5939

Article

Publisher ID: 10.1177_09636897211034464

DOI: 10.1177/09636897211034464

PMC ID: 8388229

PubMed ID: 34427495

SO-VID: e9e7367a-244d-4354-a04f-ab07531d1b25

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This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

History

Date received : 16 February 2021

Date revision received : 31 May 2021

Date accepted : 6 July 2021

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cover-date January-December 2021

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Keywords: bone marrow mesenchymal stem cells,cerebrospinal fluid,cell-based therapy,intrathecal route,matrix metalloproteinase

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Keywords: bone marrow mesenchymal stem cells, cerebrospinal fluid, cell-based therapy, intrathecal route, matrix metalloproteinase

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

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Stress signalling in stem cells

Most cited references 60

Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.

Mesenchymal stem cells: immune evasive, not immune privileged.

Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis.

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