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TISSUE-SPECIFIC STEM CELLS

The Simultaneous Treatment of MMP-2 Stimulants in Retinal Transplantation Enhances Grafted Cell Migration into the Host Retina

^aDepartment of Ophthalmology and Visual Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan;
^bDepartment of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto, Japan

Key Words. MMP-2 • Concanavalin A • 17 ß-Estradiol • Retinal transplantation

Correspondence: Michiko Mandai, M.D., Ph.D., Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto 606-8507, Japan. Telephone: +81-75-751-4717; Fax: +81-75-751-4731; e-mail: manf{at}kuhp.kyoto-u.ac.jp

Received November 23, 2005; accepted for publication June 27, 2006.


The success of functional retinal cell transplantation has been limited by the low efficiency of the transplanted cell integration into the host retina. Given that the extracellular matrix (ECM) is thought to inhibit entry and axonal outgrowth of grafted neural cells into the host retina, modulation of the ECMs in the host environment may overcome this limitation. Here, we demonstrate that matrix metalloprotease-2 (MMP-2) expression is associated with the high migratory potential of adult rat hippocampus-derived neural stem cells compared with retinal progenitor cells. In addition, MMP-2, as well as its reported inducers concanavalin A and 17ß-estradiol, can trigger the migration of retinal progenitor cells into explanted retinas. Inhibitors of MMP-2 suppressed these effects. Intense cell migration is not required for photoreceptor transplantation; however, the environment that allows the transplanted cells to integrate is most important. Migration of the transplanted cells is a good index of the acceptance of grafted cell of the host tissue. Strategies modulating the environment by MMP-2 stimulation may provide an advance in the development of retinal transplantation.

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