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多能與多能幹細胞

什麼是幹細胞?

幹細胞 具有獨特的自我更新能力,或根據體內適當的信號分化成各種類型的細胞。這些特性使幹細胞具有獨特的組織修復、替代和再生能力。由於這些特性,幹細胞已成為再生醫學和可能的幹細胞療法的寶貴研究工具。

幹細胞研究的起源可追溯至1960年代,當時James Till博士和Ernest McCulloch博士發現骨髓中的造血幹細胞1。以下是幹細胞研究的簡要年表。

幹細胞研究簡史

1963

骨髓中更新細胞的發現

    兩個兄弟姊妹之間的骨髓移植

      從小鼠胚泡中分離出胚胎幹細胞(諾貝爾獎)

        在人腦中發現成人幹細胞

          利用核轉移技術製造的小鼠胚胎幹細胞

            誘導多能幹細胞的發現(諾貝爾獎)

              使用人類胚胎幹細胞治療脊柱損傷的醫療方法

                胚胎幹細胞來自於成人幹細胞(由皮膚細胞產生的胰島素產生 Beta 細胞)

                  幹細胞的類型

                  幹細胞的三個重要特徵是其分類的基礎:

                  • 幹細胞具有無限的自我更新能力。
                  • 幹細胞是未分化的細胞,具有未特化的功能
                  • 幹細胞在適當的條件下可分化成特定的細胞類型。

                  幹細胞大致可分為多能幹細胞或多能幹細胞。

                  多能幹細胞

                  這類幹細胞包括成人幹細胞,具有自我更新或分化成特定組織或器官中存在的專門細胞類型的能力。例如,造血幹細胞可分化成各種血細胞,間充質幹細胞可分化成成骨細胞;可產生成骨細胞、肌細胞、軟骨細胞和脂肪細胞2 以及 神經幹細胞 可分化為神經元、星形細胞和少突細胞。

                  多能幹細胞的主要特徵:

                  • 少量存在於專門的組織中
                  • 主要功能是補充受損或凋亡的細胞
                  • 保持靜止狀態,直到它們感知到分化為特定類型細胞的信號
                • 多能幹細胞可分化為神經元、星形細胞和少突髮細胞。
                • 越來越多的研究正在利用多能幹細胞進行組織工程、治療白血病、為燒傷患者進行皮膚移植和美容增強。

                  多能幹細胞

                  多能幹細胞通常被稱為真正的幹細胞,因為它們具有分化成任何類型細胞系的能力。

                  胚胎幹細胞(ES細胞)

                  胚胎幹細胞是多能幹細胞,來自胚胎;來自胚泡期的內部細胞團,大約在受精後第5天。在胚胎前四個分裂期內獲得的細胞被認為是全能細胞。全能細胞具有分化為胚外組織和胚層衍生組織的能力。ESC 具有在體內無限分裂的能力,不像成體幹細胞只有在組織受損或細胞死亡時才分裂。儘管胚胎幹細胞的來源豐富且應用廣泛,但胚胎幹細胞的使用仍面臨道德挑戰。

                  圍產期幹細胞(臍帶幹細胞)

                  圍產期幹細胞來自臍帶血,是應用最廣泛的多能幹細胞。與胚胎幹細胞相比,使用圍產期幹細胞的倫理問題較少;這是因為從中分離出的組織會被棄置3。臍帶血銀行逐漸被接受為治療個人生命晚期複雜疾病的選擇。從一個人的臍帶血中分離出圍產期幹細胞,並用於移植,克服了HLA抗原不相容的問題。

                  誘導多能幹細胞(iPSCs)

                  誘導多能幹細胞(iPSCs)是人工重新編程的成人細胞,其行為與胚胎幹細胞相似。誘導多能幹細胞的優點是使用來自同一個人的體細胞,減少了移植排斥的機會。目前流行兩種誘導方法:

                  • 體細胞核移植(SCNT):
                  • 核重編程:利用轉染特定的轉錄因子(Oct3/4、Sox2、Klf4 和 c-Myc)5,對體細胞進行重編程。先進的核重編比 SCNT 更為有效,並具有重要的治療意義6.
                  表 1.存在各種幹細胞類型,包括全能細胞、多能細胞和多能細胞。

                  幹細胞研究應用

                  自我更新和分化成成熟細胞類型的能力,使幹細胞成為基礎研究的吸引目標。大部分的研究都涉及到分化因子的鑑定、基因以及存在於幹細胞龕位的環境訊號8-9。越來越多的臨床應用正在以下領域發展:

                  神經系統疾病

                  產品
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                  參考資料

                  1.
                  BECKER AJ, McCULLOCH EA, TILL JE. 1963. Cytological Demonstration of the Clonal Nature of Spleen Colonies Derived from Transplanted Mouse Marrow Cells. Nature. 197(4866):452-454. https://doi.org/10.1038/197452a0
                  2.
                  Marion NW, Mao JJ. 2006. Mesenchymal Stem Cells and Tissue Engineering.339-361. https://doi.org/10.1016/s0076-6879(06)20016-8
                  3.
                  Piskorska-Jasiulewicz MM, Witkowska-Zimny M. 2015. Perinatal sources of stem cells. Postepy Hig Med Dosw. 69327-334. https://doi.org/10.5604/17322693.1143052
                  4.
                  Brambrink T, Hochedlinger K, Bell G, Jaenisch R. 2006. ES cells derived from cloned and fertilized blastocysts are transcriptionally and functionally indistinguishable. Proceedings of the National Academy of Sciences. 103(4):933-938. https://doi.org/10.1073/pnas.0510485103
                  5.
                  Takahashi K, Yamanaka S. 2006. Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors. Cell. 126(4):663-676. https://doi.org/10.1016/j.cell.2006.07.024
                  6.
                  Shi Y. 2009. Induced Pluripotent Stem Cells, New Tools for Drug Discovery and New Hope for Stem Cell Therapies. CMP. 2(1):15-18. https://doi.org/10.2174/1874467210902010015
                  7.
                  Okita K, Ichisaka T, Yamanaka S. 2007. Generation of germline-competent induced pluripotent stem cells. Nature. 448(7151):313-317. https://doi.org/10.1038/nature05934
                  8.
                  Yokohama-Tamaki T, Otsu K, Harada H, Shibata S, Obara N, Irie K, Taniguchi A, Nagasawa T, Aoki K, Caliari SR, et al. 2015. CXCR4/CXCL12 signaling impacts enamel progenitor cell proliferation and motility in the dental stem cell niche. Cell Tissue Res. 362(3):633-642. https://doi.org/10.1007/s00441-015-2248-y
                  9.
                  Polisetti N, Zenkel M, Menzel-Severing J, Kruse FE, Schlötzer-Schrehardt U. 2016. Cell Adhesion Molecules and Stem Cell-Niche-Interactions in the Limbal Stem Cell Niche. Stem Cells. 34(1):203-219. https://doi.org/10.1002/stem.2191
                  10.
                  Ojeh N, Pastar I, Tomic-Canic M, Stojadinovic O. Stem Cells in Skin Regeneration, Wound Healing, and Their Clinical Applications. IJMS. 16(10):25476-25501. https://doi.org/10.3390/ijms161025476
                  11.
                  Lough D, Dai H, Yang M, Reichensperger J, Cox L, Harrison C, Neumeister MW. 2013. Stimulation of the Follicular Bulge LGR5+ and LGR6+ Stem Cells with the Gut-Derived Human Alpha Defensin 5 Results in Decreased Bacterial Presence, Enhanced Wound Healing, and Hair Growth from Tissues Devoid of Adnexal Structures. Plastic and Reconstructive Surgery. 132(5):1159-1171. https://doi.org/10.1097/prs.0b013e3182a48af6
                  12.
                  Kim J, Shapiro L, Flynn A. 2015. The clinical application of mesenchymal stem cells and cardiac stem cells as a therapy for cardiovascular disease. Pharmacology & Therapeutics. 1518-15. https://doi.org/10.1016/j.pharmthera.2015.02.003
                  13.
                  Patel AN, Henry TD, Quyyumi AA, Schaer GL, Anderson RD, Toma C, East C, Remmers AE, Goodrich J, Desai AS, et al. 2016. Ixmyelocel-T for patients with ischaemic heart failure: a prospective randomised double-blind trial. The Lancet. 387(10036):2412-2421. https://doi.org/10.1016/s0140-6736(16)30137-4
                  14.
                  Shuk Ke C, Elisse Y P, Andjela P, Alexandra C R, G Ian G. 2016. Current progress of human trials using stem cell therapy as a treatment for diabetes mellitus. Am. J. Stem Cells. 574–86.
                  15.
                  Xiao J, Yang R, Biswas S, Qin X, Zhang M, Deng W. Mesenchymal Stem Cells and Induced Pluripotent Stem Cells as Therapies for Multiple Sclerosis. IJMS. 16(12):9283-9302. https://doi.org/10.3390/ijms16059283
                  16.
                  Dulamea A. 2015. Mesenchymal stem cells in multiple sclerosis - translation to clinical trials. . J. Med. Life. 824–27.
                  17.
                  Keerthi N, Chimutengwende-Gordon M, Sanghani A, Khan W. 2013. The Potential of Stem Cell Therapy for Osteoarthritis and Rheumatoid Arthritis.. CSCR. 8(6):444-450. https://doi.org/10.2174/1574888x1130800062
                  18.
                  Mazzini L, Vescovi A, Cantello R, Gelati M, Vercelli A. 2016. Stem cells therapy for ALS. Expert Opinion on Biological Therapy. 16(2):187-199. https://doi.org/10.1517/14712598.2016.1116516
                  19.
                  Neirinckx V, Cantinieaux D, Coste C, Rogister B, Franzen R, Wislet-Gendebien S. 2014. Concise Review: Spinal Cord Injuries: How Could Adult Mesenchymal and Neural Crest Stem Cells Take Up the Challenge?. Stem Cells. 32(4):829-843. https://doi.org/10.1002/stem.1579
                  20.
                  Nazari H, Zhang L, Zhu D, Chader GJ, Falabella P, Stefanini F, Rowland T, Clegg DO, Kashani AH, Hinton DR, et al. 2015. Stem cell based therapies for age-related macular degeneration: The promises and the challenges. Progress in Retinal and Eye Research. 481-39. https://doi.org/10.1016/j.preteyeres.2015.06.004
                  21.
                  Merkle F, Eggan K. 2013. Modeling Human Disease with Pluripotent Stem Cells: from Genome Association to Function. Cell Stem Cell. 12(6):656-668. https://doi.org/10.1016/j.stem.2013.05.016
                  22.
                  Kitambi S, Chandrasekar. Stem cells: a model for screening, discovery and development of drugs. SCCAA.51. https://doi.org/10.2147/sccaa.s16417
                  23.
                  Braam SR, Tertoolen L, van de Stolpe A, Meyer T, Passier R, Mummery CL. 2010. Prediction of drug-induced cardiotoxicity using human embryonic stem cell-derived cardiomyocytes. Stem Cell Research. 4(2):107-116. https://doi.org/10.1016/j.scr.2009.11.004
                  24.
                  Kumari D, Swaroop M, Southall N, Huang W, Zheng W, Usdin K. 2015. High-Throughput Screening to Identify Compounds That Increase Fragile X Mental Retardation Protein Expression in Neural Stem Cells Differentiated From Fragile X Syndrome Patient-Derived Induced Pluripotent Stem Cells. 4(7):800-808. https://doi.org/10.5966/sctm.2014-0278
                  25.
                  Desbordes SC, Studer L. 2013. Adapting human pluripotent stem cells to high-throughput and high-content screening. Nat Protoc. 8(1):111-130. https://doi.org/10.1038/nprot.2012.139
                  26.
                  Dai S, Li R, Long Y, Titus S, Zhao J, Huang R, Xia M, Zheng W. 2016. One-Step Seeding of Neural Stem Cells with Vitronectin-Supplemented Medium for High-Throughput Screening Assays. J Biomol Screen. 21(10):1112-1124. https://doi.org/10.1177/1087057116670068
                  27.
                  van Sandwijk M, Bemelman F, Ten Berge I. 2013. Immunosuppressive drugs after solid organ transplantation.. Neth. J. Med.. 71281-289.
                  28.
                  Ikehara S. Grand challenges in stem cell treatments. Front. Cell Dev. Bio.. 1 https://doi.org/10.3389/fcell.2013.00002
                  29.
                  Kim D, Kim JH, Kwon Lee J, Choi SJ, Kim J, Jeun S, Oh W, Yang YS, Chang JW. 2009. Overexpression of CXC Chemokine Receptors Is Required for the Superior Glioma-Tracking Property of Umbilical Cord Blood-Derived Mesenchymal Stem Cells. Stem Cells and Development. 18(3):511-520. https://doi.org/10.1089/scd.2008.0050
                  30.
                  Aboody KS, Najbauer J, Metz MZ, D'Apuzzo M, Gutova M, Annala AJ, Synold TW, Couture LA, Blanchard S, Moats RA, et al. 2013. Neural Stem Cell-Mediated Enzyme/Prodrug Therapy for Glioma: Preclinical Studies. Science Translational Medicine. 5(184):184ra59-184ra59. https://doi.org/10.1126/scitranslmed.3005365
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