ALL STEM CELLS

Mesenchymal Stem Cells as Gene Delivery Vehicles

1. Introduction
Mesenchymal stem cells (MSCs) possess a battery of unique properties which make them ideally suited not only for cellular therapies/regenerative medicine, but also as vehicles for gene delivery in a wide array of clinical settings.
These include:
1) widespread distribution throughout the body;
2) ease of isolation and ability to be extensively expanded in culture without loss of potential;
3) the ability to differentiate into a wide array of functional cell types in vitro and in vivo;
4) they exert pronounced anti-inflammatory and immunomodulatory effects upon transplantation; and
5) the ability to home to damaged tissues, solid tumors, and metastases following in vivo administration.

In this Chapter, we will summarize the latest research in the use of MSC in regenerative medicine, focusing predominantly on their use as vehicles for transferring exogenous genes.
To highlight the immense potential these cells possess for gene therapy applications, we will
attempt to paint as broad a canvas as possible, starting with a discussion about the basic biology
of MSC, and their unique properties which combine to make MSC one of the most promising stem cell populations for use in gene therapy studies and trials. We will reveal the versatility of MSC as gene delivery vehicles by summarizing some of the most recent studies showing the ease with which MSC can be modified with a wide range of both viral and non-viral vector systems, and highlighting some of the advantages to delivering transgenes within a cellular vehicle, as opposed to administering vectors directly into the body.
We will then discuss the engineering of MSC to enhance their natural abilities to mediate repair within various tissues; one of the most popular uses of MSC to-date in the gene therapy arena. We will discuss our recent work, and that of others, using MSC to deliver coagulation factors to treat the hemophilias, with hemophilia A serving as a paradigm for how MSC could be used to deliver a therapeutic transgene, and thereby correct essentially any inherited disease. The Chapter will conclude with a discussion of MSC’s ability to selectively migrate to forming solid tumors following intravenous administration, and to actively seek out metastases at sites far removed from the primary site of the tumor. We will summarize exciting recent work showing that it is possible to exploit this property to achieve sustained, high-level expression of pro-apoptotic gene products within the tumor, obtaining greatly improved anti-tumor effects, while essentially eliminating the systemic toxicities that plague current radiation/chemotherapy-based treatments.

Orgin : http://dx.doi.org/10.5772/53240
Christopher D. Porada and Graça Almeida-Porada