Systemically administered MSCs following BMT home to in64258; amed tissues including CNS

Ref ID: 18596

Author:

J. Böhringer, M. Vaegler, R. Handgretinger, I. Müller

Author address:

University Children’s Hospital (Tubingen, DE)

Full conference title:

Annual Meeting of the EBMT, 36th

Abstract:

Human multipotent mesenchymal stromal cells (MSCs) are
increasingly used for clinical applications mainly in regenerative
medicine and immune modulation. Immunomodulatory properties of MSC are exploited in treatment of steroid refractory GvHD
following allogeneic SCT. In addition, autoinfl ammatory diseases
such as systemic sclerosis, Crohn’s disease and multiple sclerosis have shown responses to MSC in animal models and clinical
pilot trials. Application of MSC in regenerative medicine has been
largely focused on the osteogenic differentiation potential of MSC,
e.g. in osteogenesis imperfecta. However, in a growing number
of reports MSC mediate their effects in tissue regeneration by
secretion of signalling molecules and other proteins. This feature
may also be used in the treatment of patients with neurometabolic
diseases, e.g. metachromatic leukodystrophy (MLD). We show
that MSCs produce arylsulfatase A (ASA), which is the defi cient
enzyme in MLD patients. Moreover, MSCs release signifi cant
amounts of ASA into the media. In a coculture system of healthy
MSC and fi broblasts from MLD patients separated by a semipermeable membrane, ASA defi cient cells take up substantial
amounts of the enzyme. This uptake was blocked by mannose
and mannose-6-phosphate indicating that receptor mediated
processes involving the mannose-6-phosphate receptor are
important. However, in order to exert their role of enzyme replacement in the brain, MSC need to home to the CNS. This has not
been shown in humans so far, but could have great impact also
on strategies in multiple sclerosis and other autoinfl ammatory or
degenerative diseases of the CNS. Therefore, we analysed the
case of a DNA ligase IV-defi cient boy, who underwent allogeneic
bone marrow transplantation from a matched unrelated donor
and obtained MSCs from his haploidentical father for treatment
of steroid refractory hepatic and intestinal GvHD °IV four weeks
apart. Two weeks after the second application he succumbed to
GvHD and generalized aspergillosis. An autopsy was performed
and tissue samples were analysed by immunohistochemistry.
Parental MSCs were located in infl amed organs, mainly liver and
gut as well as the CNS in areas close to infi ltrates of aspergillosis.
Our results demonstrate that MSC may cross the blood-brain barrier in an infl ammatory environment and home to the CNS.

Abstract Number: P1000

Conference Year: 2010

Link to conference website: NULL

New link: NULL

Conference abstracts, posters & presentations

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