Na-Hee Yu1, So Young Chun1, Bum Soo Kim2, Tae Gyun Kwon3, Yun-Sok Ha2, Hyun Tae Kim3, Eugene Lih4, Dae Hwan Kim5, Jeongshik Kim6, Jae-Wook Chung3, Phil Hyun Song7, Eun Sang Yoo2, Sung Kwang Chung2, Dong Keun Han4. 1. 1BioMedical Research Institute, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu, 41944 Republic of Korea. 2. 2Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, 130 Dongdeok-ro, Jung-gu, Daegu, 41944 Republic of Korea. 3. 3Department of Urology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, 807 Hoguk-ro, Buk-gu, Daegu, 41404 Republic of Korea. 4. 4Department of Biomedical Science, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi 13488 Republic of Korea. 5. 5Department of Laboratory Animal Research Support Team, Yeungnam University Medical Center, 170 hyunchung-ro, Nam-gu, Daegu, 42415 Republic of Korea. 6. Department of Pathology, Central Hospital, 480 Munsu-ro, Nam-gu, Ulsan, 44667 Republic of Korea. 7. 7Department of Urology, College of Medicine, Yeungnam University, 170 Hyunchung-ro, Nam-gu, Daegu, 42415 Republic of Korea.
Abstract
BACKGROUND: Despite major progress in stem cell therapy, our knowledge of the characteristics and tissue regeneration potency of long-term transported cells is insufficient. In a previous in vitro study, we established the optimal cell transport conditions for amniotic fluid stem cells (AFSCs). In the present study, the target tissue regeneration of long-term transported cells was validated in vivo. METHODS: For renal regeneration, transported AFSCs were seeded on a poly(lactide-co-glycolide) scaffold and implanted in a partially resected kidney. The target tissue regeneration of the transported cells was compared with that of freshly harvested cells in terms of morphological reconstruction, histological microstructure reformation, immune cell infiltration, presence of induced cells, migration into remote organs, expression of inflammation/fibrosis/renal differentiation-related factors, and functional recovery. RESULTS: The kidney implanted with transported cells showed recovery of total kidney volume, regeneration of glomerular/renal tubules, low CD4/CD8 infiltration, and no occurrence of cancer during 40 weeks of observation. The AFSCs gradually disappeared and did not migrate into the liver, lung, or spleen. We observed low expression levels of pro-inflammatory cytokines and fibrotic factors; enhanced expression of the genes Wnt4, Pax2, Wt1, and Emx2; and significantly reduced blood urea nitrogen and creatinine values. There were no statistical differences between the performance of freshly harvested cells and that of the transported cells. CONCLUSION: This study demonstrates that long-term transported cells under optimized conditions can be used for cell therapy without adverse effects on stem cell characteristics, in vivo safety, and tissue regeneration potency.
BACKGROUND: Despite major progress in stem cell therapy, our knowledge of the characteristics and tissue regeneration potency of long-term transported cells is insufficient. In a previous in vitro study, we established the optimal cell transport conditions for amniotic fluid stem cells (AFSCs). In the present study, the target tissue regeneration of long-term transported cells was validated in vivo. METHODS: For renal regeneration, transported AFSCs were seeded on a poly(lactide-co-glycolide) scaffold and implanted in a partially resected kidney. The target tissue regeneration of the transported cells was compared with that of freshly harvested cells in terms of morphological reconstruction, histological microstructure reformation, immune cell infiltration, presence of induced cells, migration into remote organs, expression of inflammation/fibrosis/renal differentiation-related factors, and functional recovery. RESULTS: The kidney implanted with transported cells showed recovery of total kidney volume, regeneration of glomerular/renal tubules, low CD4/CD8 infiltration, and no occurrence of cancer during 40 weeks of observation. The AFSCs gradually disappeared and did not migrate into the liver, lung, or spleen. We observed low expression levels of pro-inflammatory cytokines and fibrotic factors; enhanced expression of the genes Wnt4, Pax2, Wt1, and Emx2; and significantly reduced blood urea nitrogen and creatinine values. There were no statistical differences between the performance of freshly harvested cells and that of the transported cells. CONCLUSION: This study demonstrates that long-term transported cells under optimized conditions can be used for cell therapy without adverse effects on stem cell characteristics, in vivo safety, and tissue regeneration potency.
Authors: Laura Perin; Sargis Sedrakyan; Stefano Giuliani; Stefano Da Sacco; Gianni Carraro; Liron Shiri; Kevin V Lemley; Michael Rosol; Sam Wu; Anthony Atala; David Warburton; Roger E De Filippo Journal: PLoS One Date: 2010-02-24 Impact factor: 3.240
Authors: Israel M Barbash; Pierre Chouraqui; Jack Baron; Micha S Feinberg; Sharon Etzion; Ariel Tessone; Liron Miller; Esther Guetta; Dov Zipori; Laurence H Kedes; Robert A Kloner; Jonathan Leor Journal: Circulation Date: 2003-08-04 Impact factor: 29.690
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