脐带血来源的成体干细胞能够分泌胰岛素
生物谷报道：在一项利用胰腺损伤或胰腺缺陷患者自身的产胰岛素细胞治疗1型糖尿病的基础研究中，医学研究人员成功从患者自身脐带血来源的干细胞获得胰岛素，这一成果刊登于上周《Cell Proliferation》杂志在线版。
文章高级作者、University of Texas Medical Branch–Galveston（UTMB）大学Randall J. Urban 博士说：“这项发现告诉我们，我们有能力利用成体干细胞产生胰岛素，帮助糖尿病患者（康复）。”文章第一作者Larry Denner教授说，医生利用成体干细胞而非胚胎干细胞进行再生医学，最终有望从个体血液中提取到干细胞，然后在实验室中大量培养，将这些细胞转化为直接形成所需器官的细胞。这种方法能够避免与移植异体细胞或器官有关的排斥反应。
形成新器官需要大量的干细胞。研究人员需要从个体移除上千个供体细胞，然后在实验室中大量培养。对于1型糖尿病患者，研究人员需要将这些细胞分化为胰岛细胞。胰岛细胞是产生胰岛素，帮助肌体利用糖，合成蛋白和储藏脂肪的细胞。Denner说之所以利用人类脐带血，是因为脐带血是新鲜成体干细胞的来源之一，很容易从剖宫产妇女获得。实验室检测成体干细胞确保这些细胞有易于分裂的倾向。然后，他们利用之前成功的方法：胚胎小鼠胰腺产生的复杂信号用于指导成体干细胞发育或“分化”为胰岛样细胞。
在实验室培养这些成体干细胞的同时，研究人员对其它细胞进行操作，使这些细胞产生SSEA-4，这个之前被认为只存在于胚胎干细胞的标志。与胚胎干细胞相似，这些成体干细胞产生C-肽段（C-peptide，胰岛素前体蛋白的一部分）和胰岛素本身。确定C-肽段非常关键，因为胰岛素在细胞生长的培养基中经常出现且常被细胞吸收，C-肽段的出现证明至少工程细胞产生或者合成了某些胰岛素。
原始出处:
Cell Proliferation，Volume 40 Issue 3 Page 367 - June 2007
To cite this article: L. Denner, Y. Bodenburg, J. G. Zhao, M. Howe, J. Cappo, R. G. Tilton, J. A. Copland, N. Forraz, C. McGuckin, R. Urban (2007)
Directed engineering of umbilical cord blood stem cells to produce C-peptide and insulin
Cell Proliferation 40 (3), 367–380.
doi:10.1111/j.1365-2184.2007.00439.x
Directed engineering of umbilical cord blood stem cells to produce C-peptide and insulin
- L. Denner**Stark Diabetes Center and McCoy Diabetes Mass Spectrometry Research Laboratory, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA,
- Y. Bodenburg**Stark Diabetes Center and McCoy Diabetes Mass Spectrometry Research Laboratory, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA,
- J. G. Zhao**Stark Diabetes Center and McCoy Diabetes Mass Spectrometry Research Laboratory, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA,
- M. Howe**Stark Diabetes Center and McCoy Diabetes Mass Spectrometry Research Laboratory, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA,
- J. Cappo*,†*Stark Diabetes Center and McCoy Diabetes Mass Spectrometry Research Laboratory, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA†Institut Universitaire de Technologie, Montpellier, France,
- R. G. Tilton**Stark Diabetes Center and McCoy Diabetes Mass Spectrometry Research Laboratory, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA,
- J. A. Copland‡‡Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, FL, USA,
- N. Forraz§§Institute of Stem Cell Biology and Regenerative Medicine, University of Newcastle Upon Tyne, UK,
- C. McGuckin§§Institute of Stem Cell Biology and Regenerative Medicine, University of Newcastle Upon Tyne, UK and
- R. Urban**Stark Diabetes Center and McCoy Diabetes Mass Spectrometry Research Laboratory, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA
- *Stark Diabetes Center and McCoy Diabetes Mass Spectrometry Research Laboratory, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, †Institut Universitaire de Technologie, Montpellier, France, ‡Department of Cancer Biology, Mayo Clinic Comprehensive Cancer Center, Jacksonville, FL, USA, and §Institute of Stem Cell Biology and Regenerative Medicine, University of Newcastle Upon Tyne, UK
- Correspondence: Larry Denner, Department of Internal Medicine, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1060, USA. Tel.: 409 772 8703; Fax: 409 772 8709; E-mail: ladenner@utmb.edu
Abstract
Abstract. Objectives: In this study, we investigated the potential of umbilical cord blood stem cell lineages to produce C-peptide and insulin. Materials and methods: Lineage negative, CD133+ and CD34+ cells were analyzed by flow cytometry to assess expression of cell division antigens. These lineages were expanded in culture and subjected to an established protocol to differentiate mouse embryonic stem cells (ESCs) toward the pancreatic phenotype. Phase contrast and fluorescence immunocytochemistry were used to characterize differentiation markers with particular emphasis on insulin and C-peptide. Results: All 3 lineages expressed SSEA-4, a marker previously reported to be restricted to the ESC compartment. Phase contrast microscopy showed all three lineages recapitulated the treatment-dependent morphological changes of ESCs as well as the temporally restricted expression of nestin and vimentin during differentiation. After engineering, each isolate contained both C-peptide and insulin, a result also obtained following a much shorter protocol for ESCs. Conclusions: Since C-peptide can only be derived from de novo synthesis and processing of pre-proinsulin mRNA and protein, we conclude that these results are the first demonstration that human umbilical cord blood-derived stem cells can be engineered to engage in de novo synthesis of insulin.
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