Cell Scooper: A Device for the Rapid Transfer of Living Cell Sheet
In this study, we developed a device that could easily, rapidly, and completely transfer cell sheets from one material to another or transplant cell sheets onto the dorsal subcutaneous tissues of rats without leaving residual cells. Because the manipulation is as simple as pipetting, technical expertise is not required to transfer cell sheets very rapidly (the transfer time was 3.7 ± 1.6 s) using the device compared with that of a conventional method using a pipette (430 ± 180 s). After transfer by the device, C2C12 skeletal myoblast sheets showed active cell metabolism, cell viability, and very high production of vascular endothelial growth factor and stromal-derived factor-1α, indicating transfer without cell damage. Cardiac cell sheets after transfer showed spontaneous and synchronous beating, indicating intact cell-cell junctions and ion channel proteins on the cell opsurface. In addition, the device allowed us to transfer C2C12 cell sheets onto soft, rugged and curved surfaces such as human hands. Furthermore, cardiac cell sheets adhered rapidly and tightly onto the dorsal subcutaneous tissues of rats. This transfer/transplantation device may be a powerful tool in cell sheet-based tissue engineering and regenerative medicine.
KeywordsMechanism Device Scooping Transfer
Upon the development of the cell-sheet transfer/transplantation device in this study, the authors referred the basic concept of SWTL, a food-handling devise, developed by Furukawakikou Co., LTd. (Niigata, Japan). The authors are grateful to the members of Furukawakikou. This work was supported by grants from a new area of Hyper Bio Assembler for 3D Cellular Systems (BioAssembler) Project, a Grant-in-Aid for Japan Society for the Promotion of Science (JSPS) Fellows (23•7758), the Global Center of Excellence Program, Multidisciplinary Education and Technology and Research Center for Regenerative Medicine (MERCREM), Innovation Center for Fusion of Advanced Technologies in the Special Coordination Funds for Promoting Science, and the High-Tech Research Center Program from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan, and JSPS through the “Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program),” initiated by the Council for Science and Technology Policy (CSTP).
- 2.Atala A, Lanza R, Thomson JA, Nerem R (2011) Principles of regenerative medicine, 2nd edn. Academic Press, San DiegoGoogle Scholar
- 3.Bolli R, Chugh AR, D’Amario D, Loughran JH, Stoddard MF, Ikram S, Beache GM, Wagner SG, Leri A, Hosoda T, Sanada F, Elmore JB, Goichberg P, Cappetta D, Solankhi NK, Fahsah I, Rokosh DG, Slaughter MS, Kajstura J, Anversa P (2011) Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet 378:1847–1857CrossRefGoogle Scholar
- 4.Zimmermann WH, Melnychenko I, Wasmeier G, Didié M, Naito H, Nixdorff U, Hess A, Budinsky L, Brune K, Michaelis B, Dhein S, Schwoerer A, Ehmke H, Eschenhagen T (2006) Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts. Nat Med 12:452–458CrossRefGoogle Scholar
- 6.Shinoka T, Breuer C (2008) Tissue-engineered blood vessels in pediatric cardiac surgery. Yale J Biol Med 81:161–166Google Scholar
- 23.Nishida K, Yamato M, Hayashida Y, Watanabe K, Maeda N, Watanabe H, Yamamoto K, Nagai S, Kikuchi A, Tano Y, Okano T (2004) Functional bioengineered corneal epithelial sheet grafts from corneal stem cells expanded ex vivo on a temperature-responsive cell culture surface. Transplantation 77:379–385CrossRefGoogle Scholar
- 36.Sekine W, Haraguchi Y, Shimizu T, Umezawa A, Okano T (2011) Thickness limitation and cell viability of multi-layered cell sheets and overcoming the diffusion limit by a porous-membrane culture insert. J Biochip Tissue Chip S2:001Google Scholar
- 37.Haraguchi Y, Matsuura K, Shimizu T, Yamato M, Okano T (2013) Simple suspension culture system of human iPS cells maintaining their pluripotency for cardiac cell sheet engineering. J Tissue Eng Regen Med. doi:10.1002/term.1761Google Scholar
- 38.Haraguchi Y, Shimizu T, Yamato M, Okano T (2012) Cell therapy and tissue engineering for cardiovascular disease. stem cells. Trans Med 1:136–141Google Scholar
- 41.Boron WF, Boulpaep EL (2003) Medical physiology. In: Radisic M, Michael VM (eds) The cardiovascular system (Chapter IV). Elsevier Science, Philadelphia, pp 421–590Google Scholar
- 43.Kawamura M, Miyagawa S, Miki K, Saito A, Fukushima S, Higuchi T, Kawamura T, Kuratani T, Daimon T, Shimizu T, Okano T, Sawa Y (2012) Feasibility, safety, and therapeutic efficacy of human induced pluripotent stem cell-derived cardiomyocyte sheets in a porcine ischemic cardiomyopathy model. Circulation 126:S29–S37CrossRefGoogle Scholar