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請用此 Handle URI 來引用此文件: http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16832
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dc.contributor.advisor楊台鴻(Tai-Horng Young)
dc.contributor.authorMing-Ying Peien
dc.contributor.author貝明穎zh_TW
dc.date.accessioned2021-06-07T23:47:28Z-
dc.date.copyright2020-09-15
dc.date.issued2020
dc.date.submitted2020-08-10
dc.identifier.citationChu, D.T., et al., Adipose Tissue Stem Cells for Therapy: An Update on the Progress of Isolation, Culture, Storage, and Clinical Application. J Clin Med, 2019. 8(7).
Sabol, R.A., et al., Therapeutic potential of adipose stem cells. 2018.
Miana, V.V. and E.A.P. Gonzalez, Adipose tissue stem cells in regenerative medicine. Ecancermedicalscience, 2018. 12: p. 822.
Pittenger, M.F., et al., Multilineage potential of adult human mesenchymal stem cells. Science, 1999. 284(5411): p. 143-7.
Oedayrajsingh-Varma, M.J., et al., Adipose tissue-derived mesenchymal stem cell yield and growth characteristics are affected by the tissue-harvesting procedure. Cytotherapy, 2006. 8(2): p. 166-77.
Lin, C.-S. and T.F. Lue, Adipose-derived stem cells: characterization and application in urology, in Adipose Stem Cells and Regenerative Medicine. 2011, Springer. p. 193-207.
Takemura, S., et al., Transplantation of adipose-derived mesenchymal stem cell sheets directly into the kidney suppresses the progression of renal injury in a diabetic nephropathy rat model. J Diabetes Investig, 2019.
Gadelkarim, M., et al., Adipose-derived stem cells: Effectiveness and advances in delivery in diabetic wound healing. Biomed Pharmacother, 2018. 107: p. 625-633.
Chang, Y.W., et al., Autologous and not allogeneic adipose-derived stem cells improve acute burn wound healing. PLoS One, 2018. 13(5): p. e0197744.
Hur, W., et al., Regeneration of full-thickness skin defects by differentiated adipose-derived stem cells into fibroblast-like cells by fibroblast-conditioned medium. Stem Cell Res Ther, 2017. 8(1): p. 92.
Hanson, C., et al., Transplanting embryonic stem cells onto damaged human corneal endothelium. World J Stem Cells, 2017. 9(8): p. 127-132.
Si, Z., et al., Adipose-derived stem cells: Sources, potency, and implications for regenerative therapies. Biomed Pharmacother, 2019. 114: p. 108765.
Nicoletti, G.F., et al., Methods and Procedures in Adipose Stem Cells: State of the Art and Perspective for Translation Medicine. Journal of Cellular Physiology, 2015. 230(3): p. 489-495.
Falanga, V., Wound healing and its impairment in the diabetic foot. The Lancet, 2005. 366(9498): p. 1736-1743.
Perez-Favila, A., et al., Current Therapeutic Strategies in Diabetic Foot Ulcers. Medicina (Kaunas), 2019. 55(11).
Cho, H., et al., Acellular and cellular approaches to improve diabetic wound healing. Adv Drug Deliv Rev, 2019. 146: p. 267-288.
Kim, S.Y., et al., Predictors for Amputation in Patients with Diabetic Foot Wound. Vasc Specialist Int, 2018. 34(4): p. 109-116.
McLennan, S.V., et al., Improving wound-healing outcomes in diabetic foot ulcers. Expert Review of Endocrinology Metabolism, 2007. 2(2): p. 205-213.
Cheng, N.C., et al., High glucose-induced reactive oxygen species generation promotes stemness in human adipose-derived stem cells. Cytotherapy, 2016. 18(3): p. 371-83.
Sada, K., et al., Hyperglycemia Induces Cellular Hypoxia through Production of Mitochondrial ROS Followed by Suppression of Aquaporin-1. PLoS One, 2016. 11(7): p. e0158619.
Czajka, A. and A.N. Malik, Hyperglycemia induced damage to mitochondrial respiration in renal mesangial and tubular cells: Implications for diabetic nephropathy. Redox Biol, 2016. 10: p. 100-107.
Kitada, K., et al., Hyperglycemia causes cellular senescence via a SGLT2- and p21-dependent pathway in proximal tubules in the early stage of diabetic nephropathy. J Diabetes Complications, 2014. 28(5): p. 604-11.
Munusamy, S. and L.A. MacMillan-Crow, Mitochondrial superoxide plays a crucial role in the development of mitochondrial dysfunction during high glucose exposure in rat renal proximal tubular cells. Free Radic Biol Med, 2009. 46(8): p. 1149-57.
Nishikawa, T., et al., Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature, 2000. 404: p. 787-790.
Liu, Y., et al., The effect of high glucose on the biological characteristics of nucleus pulposus-derived mesenchymal stem cells. Cell Biochemistry and Function, 2020. 38(2): p. 130-140.
Khan, M., et al., Growth Factor Preconditioning Increases the Function of Diabetes-Impaired Mesenchymal Stem Cells. Stem Cells and Development, 2011. 20: p. 67-75.
Vincent, A.M., et al., SOD2 protects neurons from injury in cell culture and animal models of diabetic neuropathy. Exp Neurol, 2007. 208(2): p. 216-27.
X., S., et al., Protection of cardiac mitochondria by overexpression of MnSOD reduces diabetic cardiomyopathy. Diabetes, 2006. 55: p. 798-805.
Kowluru, R.A., et al., Overexpression of mitochondrial superoxide dismutase in mice protects the retina from diabetes-induced oxidative stress. Free Radic Biol Med, 2006. 41(8): p. 1191-6.
El-Ftesi, S., et al., Aging and diabetes impair the neovascular potential of adipose-derived stromal cells. Plast Reconstr Surg, 2009. 123(2): p. 475-85.
You, H.J. and S.K. Han, Cell therapy for wound healing. J Korean Med Sci, 2014. 29(3): p. 311-9.
Han, S.K., H.S. Kim, and W.K. Kim, Efficacy and safety of fresh fibroblast allografts in the treatment of diabetic foot ulcers. Dermatol Surg, 2009. 35(9): p. 1342-8.
Hocking, A.M., Mesenchymal Stem Cell Therapy for Cutaneous Wounds. Advances in Wound Care, 2012. 1(4): p. 166-171.
You, H.J., et al., Treatment of diabetic foot ulcers using cultured allogeneic keratinocytes--a pilot study. Wound Repair Regen, 2012. 20(4): p. 491-9.
Han, S.-K., H.-R. Kim, and W.-K. Kim, The treatment of diabetic foot ulcers with uncultured, processed lipoaspirate cells: A pilot study. Wound Repair and Regeneration, 2010. 18(4): p. 342-348.
Han, S.-K., K.-J. Choi, and W.-K. Kim, Clinical Application of Fresh Fibroblast Allografts for the Treatment of Diabetic Foot Ulcers: A Pilot Study. Plastic and Reconstructive Surgery, 2004. 114(7): p. 1783-1789.
Kwon, D.S., et al., Treatment with bone marrow-derived stromal cells accelerates wound healing in diabetic rats. International Wound Journal, 2008. 5(3): p. 453-463.
Kuo, Y.-R., et al., Adipose-Derived Stem Cells Accelerate Diabetic Wound Healing through the Induction of Autocrine and Paracrine Effects. Cell Transplantation, 2016. 25(1): p. 71-81.
Cianfarani, F., et al., Diabetes impairs adipose tissue–derived stem cell function and efficiency in promoting wound healing. Wound Repair and Regeneration, 2013. 21(4): p. 545-553.
Jeong, H.J., et al., Hypoxia-induced IL-6 production is associated with activation of MAP kinase, HIF-1, and NF-kappaB on HEI-OC1 cells. Hear Res, 2005. 207(1-2): p. 59-67.
Shweiki, D., et al., Vascular Endothelial Growth-Factor Induced by Hypoxia May Mediate Hypoxia-Initiated Angiogenesis. Nature, 1992. 359: p. 843-845.
James, G.A., et al., Biofilms in chronic wounds. Wound Repair Regen, 2008. 16(1): p. 37-44.
Harding, K.G., H.L. Morris, and G.K. Patel, Healing chronic wounds. British Medical Journal, 2002. 324: p. 160-163.
Han, Y., et al., Mesenchymal Stem Cells for Regenerative Medicine. Cells, 2019. 8(8).
Cramer, C., et al., Persistent High Glucose Concentrations Alter the Regenerative Potential of Mesenchymal Stem Cells. Stem Cells Dev, 2010. 19: p. 1875-84.
Stolzing, A., N. Coleman, and A. Scutt, Glucose-induced replicative senescence in mesenchymal stem cells. Rejuv Res 2006. 9: p. 31-35.
Donath, M.Y., et al., Hyperglycemia-induced beta-cell apoptosis in pancreatic islets of Psammomys obesus during development of diabetes. Diabetes, 1999. 48: p. 738-744.
Penhallow, K., A review of studies that examine the impact of infection on the normal wound-healing process. Journal of Wound Care, 2005. 14(3): p. 123-126.
C.Robson, M., WOUND INFECTION_A Failure of Wound Healing Caused by an Imbalance of Bacteria. 1997. 77(3): p. 637-650.
Gu, J.H., et al., Neovascular potential of adipose-derived stromal cells (ASCs) from diabetic patients. Wound Repair Regen, 2012. 20(2): p. 243-52.
Song, S.Y., H.M. Chung, and J.H. Sung, The pivotal role of VEGF in adipose-derived-stem-cell-mediated regeneration. Expert Opin Biol Ther, 2010. 10(11): p. 1529-37.
Thangarajah, H., et al., The molecular basis for impaired hypoxia-induced VEGF expression in diabetic tissues. P Natl Acad Sci USA 2009. 106: p. 13505-10.
Zeng, Z., et al., Arnebin-1 promotes angiogenesis by inducing eNOS, VEGF and HIF-1α expression through the PI3K-dependent pathway. Int J Mol Med, 2015. 36(3): p. 685-697.
Ceradini, D.J., et al., Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nature Medicine, 2004. 10(8): p. 858-864.
Catrina, S.-B., et al., Hyperglycemia Regulates Hypoxia-Inducible Factor-1α Protein Stability and Function. Diabetes, 2004. 53(12): p. 3226.
Ben Nasr, M., et al., Co-transplantation of autologous MSCs delays islet allograft rejection and generates a local immunoprivileged site. Acta Diabetol, 2015. 52(5): p. 917-27.
Wiegering, V., et al., Comparison of Immune Reconstitution After Allogeneic Versus Autologous Stem Cell Transplantation in 182 Pediatric Recipients. Journal of pediatric hematology/oncology, 2019. 41: p. 302-307.
dc.identifier.urihttp://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16832-
dc.description.abstract脂肪幹細胞為近年來最容易取得且數量豐富的幹細胞,應用上也越趨多元化。常用於組織修復、燒燙傷、抗衰老、關節保健、軟組織填補。對於有慢性傷口癒合延遲問題的病人,自體幹細胞移植成為除了常規治療以外的另一種治療方式。許多研究指出,糖尿病病人的高血糖症會對器官、組織與細胞造成損害,進而引發糖尿病併發症。再者,長期處於高糖環境下的自體幹細胞也會降低其對傷口修復與組織再生的能力。由於傷口的延遲癒合,在這期間容易造成傷口感染,並增加傷口的發炎程度。
本研究探討經由低糖處理後的自體脂肪幹細胞對糖尿病傷口的治療。藉由改變糖尿病鼠脂肪幹細胞培養的微環境,使自體脂肪幹細胞修復傷口的能力獲得改善。我們發現在體外實驗中,低糖環境能夠促進糖尿病脂肪幹細胞的增殖與減少細胞衰老的現象。對於曾浸潤在高糖環境中的糖尿病鼠脂肪幹細胞,經由低糖環境培養一週後,能夠比沒有經過低糖處理的糖尿病鼠脂肪幹細胞具有更佳的傷口修復能力,並促進血管新生與成纖維細胞的增生。因此,自體脂肪幹細胞經由低糖環境培養後,對於糖尿病傷口修復可能為一種可行的療法。
zh_TW
dc.description.abstractAdipose-derived stem cells (ASCs) have been the most readily available and abundant stem cells in recent years, and the applications of ASC are becoming more and more diverse, such as tissue repair, burns, anti-aging, joint health, and soft tissue filling. For patients with chronic wound healing delays, autologous stem cell transplantation has become another treatment in addition to conventional treatment.
Several studies suggested that hyperglycemia in diabetic patients will damage organs and tissues, and cause diabetes complications. Furthermore, autologous stem cells that have been in a high-glucose environment for a long time will also reduce the ability of repair wounds. Due to the delayed healing of the wound, it is easy to cause wound infection and increase the degree of inflammation of the wound.
In order to study the treatment of diabetic wounds with autologous ASCs treated with low-glucose environment, we cultured diabetic murine ASC in low-glucose for a week to improve ASCs to repair wounds. We found that ASCs cultured in low-glucose could promote the cell proliferation and reduce the cell aging in vitro. Moreover, they could have better wound repairing ability than ASCs cultured in high-glucose, and promote angiogenesis and fibroblast proliferation in vivo. Therefore, after autologous ASCs are cultured in a low-sugar environment, it may be a feasible treatment for diabetic wound repair.
en
dc.description.provenanceMade available in DSpace on 2021-06-07T23:47:28Z (GMT). No. of bitstreams: 1
U0001-1008202001574500.pdf: 3325923 bytes, checksum: b756e204234368802485a5daa28393da (MD5)
Previous issue date: 2020
en
dc.description.tableofcontents致謝 1
中文摘要 2
Abstract 3
Contents 5
Figure Contents 7
Table Contents 8
Chapter 1: Introduction 9
1.1 Regenerative medicine 9
1.2 Adipose-derived stem cells (ADSCs) 9
1.3 Wound healing in diabetes mellitus (DM) 11
1.4 Research on the treatment of diabetic wounds 13
1.5 Effect of hyperglycemia on cells 13
1.6 Cell therapy for diabetic wound 14
1.7 Motivation and Aim 16
Chapter 2: Materials and methods 17
2.1 Animal model 17
2.2 Murine ADSC isolation and expansion 17
2.3 Flow cytometry analysis 18
2.4 Multipotential differentiation of murine ADSCs 18
2.5 Cell population doubling in LG/HG environment 19
2.6 SA-β-gal analysis 20
2.7 Mice surgery and tissue harvesting 20
2.8 Hematoxylin and eosin stain (H E) 21
2.9Masson Trichrome Stain 21
2.10 Immunohistochemistry (IHC) 22
2.11 Real-time quantitative polymerase chain reaction (RT-qPCR) 23
2.12 Statistical analysis 23
Chapter 3: Results 25
3-1 Murine ADSCs characterization and differentiation 25
3-2 Effect of glucose on murine ADSCs growth 27
3-3 Murine ADSCs senesce faster in a high-glucose environment 28
3-4 Wound healing ability of murine ADSCs in HG/LG environment 29
3-5 Histology of db/db wound 31
3-6 RT-qPCR analysis of gene expression 33
Chapter 4: Discussion and Conclusion 34
Figure 38
Reference 54
dc.language.isoen
dc.subject細胞治療zh_TW
dc.subject脂肪幹細胞zh_TW
dc.subject傷口修復zh_TW
dc.subject糖尿病zh_TW
dc.subject葡萄糖zh_TW
dc.subjectAdipose-derived stem cellsen
dc.subjectDiabetes mellitusen
dc.subjectWound healingen
dc.subjectD-glucoseen
dc.subjectCell therapyen
dc.title高低糖環境對糖尿病脂肪幹細胞傷口癒合能力之研究zh_TW
dc.titleWound healing ability of diabetic adipose-derived stem cells in high or low D-glucose environmenten
dc.typeThesis
dc.date.schoolyear108-2
dc.description.degree碩士
dc.contributor.coadvisor鄭乃禎(Nai-Chen Cheng)
dc.contributor.oralexamcommittee陳克誠(Ke-Cheng Chen)
dc.subject.keyword脂肪幹細胞,傷口修復,糖尿病,細胞治療,葡萄糖,zh_TW
dc.subject.keywordAdipose-derived stem cells,Wound healing,Diabetes mellitus,Cell therapy,D-glucose,en
dc.relation.page57
dc.identifier.doi10.6342/NTU202002757
dc.rights.note未授權
dc.date.accepted2020-08-11
dc.contributor.author-college工學院zh_TW
dc.contributor.author-dept醫學工程學研究所zh_TW
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