IngentaConnect Mesenchymal stem cells (MSC) as therapeutic cytoreagents for gene...

Authors: Hamada, Hirofumi; Kobune, Masayoshi; Nakamura, Kiminori¹; Kawano, Yutaka; Kato, Kazunori¹; Honmou, Osamu²; Houkin, Kiyohiro²; Matsunaga, Takuya³; Niitsu, Yoshiro³

Source: Cancer Science, Volume 96, Number 3, March 2005 , pp. 149-156(8)

Publisher: Blackwell Publishing

Abstract:

We developed human mesenchymal stem cell (MSC) lines that could differentiate into various tissue cells including bone, neural cells, bone marrow (BM) stromal cells supporting the growth of hematopoietic stem cell (HSC), and so-called ‘tumor stromal cells’ mixing with tumor cells. We investigated the applicability of MSC as therapeutic cell transplanting reagents (cytoreagents). Telomerized human BM derived stromal cells exhibited a prolonged lifespan and supported the growth of hematopoietic clonogenic cells. The gene transfer of Indian hedgehog (Ihh) remarkably enhanced the HSC expansion supported by the human BM stromal cells. Gene-modified MSC are useful as therapeutic tools for brain tissue damage (e.g. brain infarction) and malignant brain neoplasms. MSC transplantation protected the brain tissue from acute ischemic damage in the midcerebral artery occlusion (MCAO) animal model. Brain-derived neurotrophic factor (BDNF)-gene transduction further enhanced the protective efficacy against the ischemic damage. MSC possessed excellent migratory ability and exerted inhibitory effects on the proliferation of glioma cells. Gene-modification of MSC with therapeutic cytokines clearly augmented the antitumor effect and prolonged the survival of tumor-bearing animals. Gene therapy employing MSC as a tissue-protecting and targeting cytoreagent would be a promising approach. (Cancer Sci 2005; 96: 149–156)

Document Type: Research article

DOI: 10.1111/j.1349-7006.2005.00032.x

Affiliations: 1: Department of Molecular Medicine, 2: Department of Neurosurgery, and 3: Fourth Department of Internal Medicine, Sapporo Medical University, Sapporo 060–8556, Japan

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Mesenchymal stem cells (MSC) as therapeutic cytoreagents for gene therapy