CardiacPatch
BMES 212- Body Synthetic, Winter 2008 Project
Nanotechnology-Based
Cell Sheet Engineering for Regenerative Medicine
- In order to avoid several complications resulted from biodegradable scaffolds or single cell injection, researchers have developed “cell sheet engineering” by utilizing nanotechnology-based temperature-responsive culture dishes.[1]
- Since temperature-responsive polymers are covalently grafted on the dishes, various types of cells adhere and proliferate on them at 37°C, but are spontaneously detached only by reducing temperature below 32°C without any need for proteolytic enzyme. All the confluent cells are noninvasively harvested as a single contiguous cell sheets with intact cell-cell junctions and deposited extracellular matrix. We have utilized these harvested cell sheets for various tissue reconstruction including ocular surfaces, periodontal ligament, cardiac patches as well as bladder.[1]
- Single cell suspension injection sometimes works in the transplantation of stem cells to small animals such as rats and mice, since the targeted tissue size is too small. However, single cell suspension injection is not applicable for large tissue reconstruction.[1]
- It has been shown that only a few percents of injected cells can be integrated to host tissues. It is apparent that we currently lack ways of tissue reconstruction. This is the precise reason why we have proposed “cell sheet engineering”. As biodegradable polymers are the key technology in the first generation tissue engineering, we introduce of temperature-responsive culture dishes for the next generation.[1]
- Recent progress in cell transplantation therapy to repair impaired hearts has encouraged further attempts to bioengineer three-dimensional heart tissue from cultured cardiac myocytes. Cardiac tissue engineering has been also pursued utilizing conventional technology with biodegradable polymer scaffolds as a temporary extracellular matrix. However, the inflexible and bulky properties of the scaffolds significantly hamper the dynamic pulsation of cardiac myocytes as mentioned above.[1]
Fig. 3 Cardiac patch cell sheet engineering. Cardiac myocyte sheets are
harvested from temperature-responsive culture dishes. Four cell sheets are then
stratified and transplanted to ischemic hearts as cardiac patches.
- Multiple cell sheet transplantation has been examined to regenerate thick tissues such as smooth muscle and cardiac tissue. Cell sheets harvested from temperature-responsive culture dishes by reducing temperature were stratified in vitro, then subjected to transplantation.[1]
- The
synthetic materials currently available for the repair of
cardiac defects are nonviable, do not grow as the child develops, and
do not
contract synchronously with the heart. So they developed a beating patch by
seeding fetal
cardiomyocytes in a biodegradable scaffold in vitro. The seeded patches
survived
in the right ventricular outflow tract of adult rats.
- Cultured fetal or adult rat heart cells (1 × 106 cells) were seeded into a gelatin sponge (15 × 15 × 1 mm), and the cell number was expanded in culture for 1 or 3 weeks, respectively.[2]
- The free wall of the right ventricular outflow tract in syngeneic adult rats was resected and repaired with either unseeded patches or patches seeded with either fetal or adult cardiomyocytes (n = 10 for each group). The patches were examined histologically over a 12- week period.[2]
- A gelatin patch was used to replace the right ventricular outflow tract in syngeneic rats. The seeded cells survived in the right ventricular outflow tract after the scaffold dissolved 12 weeks after implantation.[2]
Fig 1. Adult heart cell-seeded patch in vitro. Hematoxylin and eosin staining
of vertical sections after culturing for 3 weeks (A, 100×; B, 400×).
the cultured cells was found.
References
[1] Yamato, Masayuki, Nanotechnology Bases Cell-Sheet Engineering for Regenerative Medicine, Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Japan.
http://ieeexplore.ieee.org/iel5/10597/33507/01589999.pdf?arnumber=1589999
[2] Yamato, Masayuki, Okano Teruo, Cell Sheet Engineering, Materials Today, May 2004
http://www.nanonet.go.jp/english/mailmag/2006/062a.html
Through Mary Ann Liebert inc.:
http://www.liebertonline.com/doi/pdf/10.1089/ten.2005.11.1678
