Beneficial and detrimental impact of transplanted canine adipose-derived stem cells in a virus-induced demyelinating mouse model.

Hansmann, F; Jungwirth, N; Zhang, N; Skripuletz, T; Stein, Veronika Maria; Tipold, A; Stangel, M; Baumgärtner, W (2018). Beneficial and detrimental impact of transplanted canine adipose-derived stem cells in a virus-induced demyelinating mouse model. Veterinary immunology and immunopathology, 202, pp. 130-140. Elsevier 10.1016/j.vetimm.2018.07.005

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In recent years stem cell therapies have been broadly applied in various disease models specifically immune mediated and degenerative diseases. Whether adipose-derived stem cells might represent a useful therapeutic option in virus-triggered central nervous system diseases has not been investigated so far. Theiler's murine encephalomyelitis (TME) and canine distemper encephalitis are established, virus-mediated animal models sharing many similarities with multiple sclerosis (MS). Canine adipose-derived stem cells (ASC) were selected since dogs might serve as an important translational model for further therapeutic applications. The aim of the present study was to investigate whether canine ASC influence clinical signs, axonal damage, demyelination and inflammation during TME. ASC were transplanted intravenously (iv) or intra-cerebroventricularly (icv) at 7 (early) or 42 (late) days post infection (dpi) in TME virus (TMEV) infected mice. TMEV/ASC iv animals transplanted at 7dpi displayed a transient clinical deterioration in rotarod performance compared to TMEV/control animals. Worsening of clinical signs was associated with significantly increased numbers of microglia/macrophages and demyelination in the spinal cord. In contrast, late transplantation had no influence on clinical findings of TMEV-infected animals. However, late TMEV/ASC iv transplanted animals showed reduced axonal damage compared to TMEV/control animals. Screening of spinal cord and peripheral organs for transplanted ASC revealed no positive cells. Surprisingly, iv transplanted animals showed pulmonary follicular aggregates consisting of T- and B-lymphocytes. Thus, our data suggest that following intravenous application, the lung as priming organ for lymphocytes seems to play a pivotal role in the pathogenesis of TME. Consequences of T-lymphocyte priming in the lung depend on the disease phase and may be responsible for disease modifying effects of ASC.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV) > DKV - Clinical Neurology
05 Veterinary Medicine > Department of Clinical Veterinary Medicine (DKV)

UniBE Contributor:

Stein, Veronika Maria

Subjects:

600 Technology > 630 Agriculture

ISSN:

0165-2427

Publisher:

Elsevier

Language:

English

Submitter:

Veronika Maria Stein

Date Deposited:

13 May 2019 11:14

Last Modified:

25 Oct 2019 02:05

Publisher DOI:

10.1016/j.vetimm.2018.07.005

PubMed ID:

30078587

BORIS DOI:

10.7892/boris.127366

URI:

https://boris.unibe.ch/id/eprint/127366

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