Skip to main content
SpringerLink
Log in

Production of Good Manufacturing Practice-Grade Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells for Therapeutic Use

  • Protocol
  • First Online:
Stem Cells and Good Manufacturing Practices

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1283))

Abstract

Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) are multipotent stem cells that can be differentiated into several specific cell types such as adipocytes, osteoblasts, and chondroblasts. They also were demonstrated to trans-differentiate into other cell lineages such as muscle cells and neurons. Thus, they are considered a promising stem cell source for therapeutic use. Here, we describe a method for production of good manufacturing practice-grade human UCB-MSCs for therapeutic use. The obtained UCB-MSCs are free of allogenous or xenogenous proteins. In addition, these MSCs could maintain the MSC phenotype in long-term culture.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Friedenstein AJ, Piatetzky S II, Petrakova KV (1966) Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol 16(3):381–390

    CAS  PubMed  Google Scholar 

  2. Friedenstein AJ, Deriglasova UF, Kulagina NN, Panasuk AF, Rudakowa SF, Luria EA, Ruadkow IA (1974) Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method. Exp Hematol 2(2):83–92

    CAS  PubMed  Google Scholar 

  3. Prockop DJ, Sekiya I, Colter DC (2001) Isolation and characterization of rapidly self-renewing stem cells from cultures of human marrow stromal cells. Cytotherapy 3(5):393–396. doi:10.1080/146532401753277229

    Article  CAS  PubMed  Google Scholar 

  4. Jones EA, Kinsey SE, English A, Jones RA, Straszynski L, Meredith DM, Markham AF, Jack A, Emery P, McGonagle D (2002) Isolation and characterization of bone marrow multipotential mesenchymal progenitor cells. Arthritis Rheum 46(12):3349–3360. doi:10.1002/art.10696

    Article  PubMed  Google Scholar 

  5. Bunnell BA, Flaat M, Gagliardi C, Patel B, Ripoll C (2008) Adipose-derived stem cells: isolation, expansion and differentiation. Methods 45(2):115–120. doi:10.1016/j.ymeth.2008.03.006

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Boquest AC, Shahdadfar A, Brinchmann JE, Collas P (2006) Isolation of stromal stem cells from human adipose tissue. Methods Mol Biol 325:35–46. doi:10.1385/1-59745-005-7:35

    PubMed  Google Scholar 

  7. Ulrich D, Muralitharan R, Gargett CE (2013) Toward the use of endometrial and menstrual blood mesenchymal stem cells for cell-based therapies. Expert Opin Biol Ther 13(10):1387–1400. doi:10.1517/14712598.2013.826187

    Article  CAS  PubMed  Google Scholar 

  8. Lee OK, Kuo TK, Chen WM, Lee KD, Hsieh SL, Chen TH (2004) Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood 103(5):1669–1675. doi:10.1182/blood-2003-05-1670

    Article  CAS  PubMed  Google Scholar 

  9. Phuc PV, Ngoc VB, Lam DH, Tam NT, Viet PQ, Ngoc PK (2012) Isolation of three important types of stem cells from the same samples of banked umbilical cord blood. Cell Tissue Bank 13(2):341–351. doi:10.1007/s10561-011-9262-4

    Article  CAS  PubMed  Google Scholar 

  10. Gong W, Han Z, Zhao H, Wang Y, Wang J, Zhong J, Wang B, Wang S, Wang Y, Sun L, Han Z (2012) Banking human umbilical cord-derived mesenchymal stromal cells for clinical use. Cell Transplant 21(1):207–216. doi:10.3727/096368911x586756

    Article  PubMed  Google Scholar 

  11. Kosmacheva SM, Seviaryn IN, Goncharova NV, Petyovka NV, Potapnev MP (2011) Hepatogenic potential of human bone marrow and umbilical cord blood mesenchymal stem cells. Bull Exp Biol Med 151(1):142–149

    Article  CAS  PubMed  Google Scholar 

  12. Hong SH, Gang EJ, Jeong JA, Ahn C, Hwang SH, Yang IH, Park HK, Han H, Kim H (2005) In vitro differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocyte-like cells. Biochem Biophys Res Commun 330(4):1153–1161. doi:10.1016/j.bbrc.2005.03.086

    Article  CAS  PubMed  Google Scholar 

  13. Jin HJ, Nam HY, Bae YK, Kim SY, Im IR, Oh W, Yang YS, Choi SJ, Kim SW (2010) GD2 expression is closely associated with neuronal differentiation of human umbilical cord blood-derived mesenchymal stem cells. Cell Mol Life Sci 67(11):1845–1858. doi:10.1007/s00018-010-0292-z

    Article  CAS  PubMed  Google Scholar 

  14. Yang S, Xue DD, Wu B, Sun HM, Li XS, Dong F, Li WS, Ji FQ, Zhou DS (2013) Pleiotrophin is involved in the amniotic epithelial cell-induced differentiation of human umbilical cord blood-derived mesenchymal stem cells into dopaminergic neuron-like cells. Neurosci Lett 539:86–91. doi:10.1016/j.neulet.2013.01.046

    Article  CAS  PubMed  Google Scholar 

  15. Jeong JA, Gang EJ, Hong SH, Hwang SH, Kim SW, Yang IH, Ahn C, Han H, Kim H (2004) Rapid neural differentiation of human cord blood-derived mesenchymal stem cells. Neuroreport 15(11):1731–1734

    Article  CAS  PubMed  Google Scholar 

  16. Fang CH, Jin J, Joe JH, Song YS, So BI, Lim SM, Cheon GJ, Woo SK, Ra JC, Lee YY, Kim KS (2012) In vivo differentiation of human amniotic epithelial cells into cardiomyocyte-like cells and cell transplantation effect on myocardial infarction in rats: comparison with cord blood and adipose tissue-derived mesenchymal stem cells. Cell Transplant 21(8):1687–1696. doi:10.3727/096368912x653039

    Article  PubMed  Google Scholar 

  17. Roura S, Farre J, Hove-Madsen L, Prat-Vidal C, Soler-Botija C, Galvez-Monton C, Vilalta M, Bayes-Genis A (2010) Exposure to cardiomyogenic stimuli fails to transdifferentiate human umbilical cord blood-derived mesenchymal stem cells. Basic Res Cardiol 105(3):419–430. doi:10.1007/s00395-009-0081-8

    Article  PubMed  Google Scholar 

  18. Nishiyama N, Miyoshi S, Hida N, Uyama T, Okamoto K, Ikegami Y, Miyado K, Segawa K, Terai M, Sakamoto M, Ogawa S, Umezawa A (2007) The significant cardiomyogenic potential of human umbilical cord blood-derived mesenchymal stem cells in vitro. Stem Cells 25(8):2017–2024. doi:10.1634/stemcells.2006-0662

    Article  CAS  PubMed  Google Scholar 

  19. Wang M, Yang Y, Yang D, Luo F, Liang W, Guo S, Xu J (2009) The immunomodulatory activity of human umbilical cord blood-derived mesenchymal stem cells in vitro. Immunology 126(2):220–232. doi:10.1111/j.1365-2567.2008.02891.x

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Yoo KH, Jang IK, Lee MW, Kim HE, Yang MS, Eom Y, Lee JE, Kim YJ, Yang SK, Jung HL, Sung KW, Kim CW, Koo HH (2009) Comparison of immunomodulatory properties of mesenchymal stem cells derived from adult human tissues. Cell Immunol 259(2):150–156. doi:10.1016/j.cellimm.2009.06.010

    Article  CAS  PubMed  Google Scholar 

  21. Shi D, Wang D, Li X, Zhang H, Che N, Lu Z, Sun L (2012) Allogeneic transplantation of umbilical cord-derived mesenchymal stem cells for diffuse alveolar hemorrhage in systemic lupus erythematosus. Clin Rheumatol 31(5):841–846. doi:10.1007/s10067-012-1943-2

    Article  PubMed  Google Scholar 

  22. Lee H, Bae JS, Jin HK (2010) Human umbilical cord blood-derived mesenchymal stem cells improve neurological abnormalities of Niemann-Pick type C mouse by modulation of neuroinflammatory condition. J Vet Med Sci 72(6):709–717

    Article  CAS  PubMed  Google Scholar 

  23. Gregoire-Gauthier J, Selleri S, Fontaine F, Dieng MM, Patey N, Despars G, Beausejour CM, Haddad E (2012) Therapeutic efficacy of cord blood-derived mesenchymal stromal cells for the prevention of acute graft-versus-host disease in a xenogenic mouse model. Stem Cells Dev 21(10):1616–1626. doi:10.1089/scd.2011.0413

    Article  CAS  PubMed  Google Scholar 

  24. Lv YT, Zhang Y, Liu M, Qiuwaxi JN, Ashwood P, Cho SC, Huan Y, Ge RC, Chen XW, Wang ZJ, Kim BJ, Hu X (2013) Transplantation of human cord blood mononuclear cells and umbilical cord-derived mesenchymal stem cells in autism. J Transl Med 11:196. doi:10.1186/1479-5876-11-196

    Article  PubMed Central  PubMed  Google Scholar 

  25. Jin JL, Liu Z, Lu ZJ, Guan DN, Wang C, Chen ZB, Zhang J, Zhang WY, Wu JY, Xu Y (2013) Safety and efficacy of umbilical cord mesenchymal stem cell therapy in hereditary spinocerebellar ataxia. Curr Neurovasc Res 10(1):11–20

    Article  CAS  PubMed  Google Scholar 

  26. Li XY, Zheng ZH, Li XY, Guo J, Zhang Y, Li H, Wang YW, Ren J, Wu ZB (2013) Treatment of foot disease in patients with type 2 diabetes mellitus using human umbilical cord blood mesenchymal stem cells: response and correction of immunological anomalies. Curr Pharm Des 19(27):4893–4899

    Article  CAS  PubMed  Google Scholar 

  27. Han H, Chang SK, Chang JJ, Hwang SH, Han SH, Chun BH (2011) Intrathecal injection of human umbilical cord blood-derived mesenchymal stem cells for the treatment of basilar artery dissection: a case report. J Med Case Reports 5:562. doi:10.1186/1752-1947-5-562

    Article  PubMed Central  Google Scholar 

  28. Yang SS, Kim NR, Park KB, Do YS, Roh K, Kang KS, Kim DI (2013) A phase I study of human cord blood-derived mesenchymal stem cell therapy in patients with peripheral arterial occlusive disease. Int J Stem Cells 6(1):37–44

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Kocaoemer A, Kern S, Kluter H, Bieback K (2007) Human AB serum and thrombin-activated platelet-rich plasma are suitable alternatives to fetal calf serum for the expansion of mesenchymal stem cells from adipose tissue. Stem Cells 25(5):1270–1278. doi:10.1634/stemcells.2006-0627

    Article  CAS  PubMed  Google Scholar 

  30. Bieback K, Hecker A, Kocaomer A, Lannert H, Schallmoser K, Strunk D, Kluter H (2009) Human alternatives to fetal bovine serum for the expansion of mesenchymal stromal cells from bone marrow. Stem Cells 27(9):2331–2341. doi:10.1002/stem.139

    Article  CAS  PubMed  Google Scholar 

  31. Jonsdottir-Buch SM, Lieder R, Sigurjonsson OE (2013) Platelet lysates produced from expired platelet concentrates support growth and osteogenic differentiation of mesenchymal stem cells. PLoS One 8(7):e68984. doi:10.1371/journal.pone.0068984

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Rauch C, Feifel E, Amann EM, Spotl HP, Schennach H, Pfaller W, Gstraunthaler G (2011) Alternatives to the use of fetal bovine serum: human platelet lysates as a serum substitute in cell culture media. ALTEX 28(4):305–316

    Article  PubMed  Google Scholar 

  33. Blande IS, Bassaneze V, Lavini-Ramos C, Fae KC, Kalil J, Miyakawa AA, Schettert IT, Krieger JE (2009) Adipose tissue mesenchymal stem cell expansion in animal serum-free medium supplemented with autologous human platelet lysate. Transfusion 49(12):2680–2685. doi:10.1111/j.1537-2995.2009.02346.x

    Article  PubMed  Google Scholar 

  34. Ding Y, Yang H, Feng JB, Qiu Y, Li DS, Zeng Y (2013) Human umbilical cord-derived MSC culture: the replacement of animal sera with human cord blood plasma. In Vitro Cell Dev Biol Anim 49(10):771–777. doi:10.1007/s11626-013-9663-8

    Article  CAS  PubMed  Google Scholar 

  35. Shetty P, Bharucha K, Tanavde V (2007) Human umbilical cord blood serum can replace fetal bovine serum in the culture of mesenchymal stem cells. Cell Biol Int 31(3):293–298. doi:10.1016/j.cellbi.2006.11.010

    Article  CAS  PubMed  Google Scholar 

  36. Ma HY, Yao L, Yu YQ, Li L, Ma L, Wei WJ, Lu XM, Du LL, Jin YN (2012) An effective and safe supplement for stem cells expansion ex vivo: cord blood serum. Cell Transplant 21(5):857–869. doi:10.3727/096368911x612486

    Article  PubMed  Google Scholar 

  37. Murphy MB, Blashki D, Buchanan RM, Yazdi IK, Ferrari M, Simmons PJ, Tasciotti E (2012) Adult and umbilical cord blood-derived platelet-rich plasma for mesenchymal stem cell proliferation, chemotaxis, and cryo-preservation. Biomaterials 33(21):5308–5316. doi:10.1016/j.biomaterials.2012.04.007

    Article  CAS  PubMed  Google Scholar 

  38. Escobedo-Lucea C, Bellver C, Gandia C, Sanz-Garcia A, Esteban FJ, Mirabet V, Forte G, Moreno I, Lezameta M, Ayuso-Sacido A, Garcia-Verdugo JM (2013) A xenogeneic-free protocol for isolation and expansion of human adipose stem cells for clinical uses. PLoS One 8(7):e67870. doi:10.1371/journal.pone.0067870

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8(4):315–317. doi:10.1080/14653240600855905

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This study was supported by the grant number DTDL.2012-G/23, Ministry of Science and Technology, Vietnam.

Author information

Authors and Affiliations

  1. Laboratory of Stem Cell Research and Application, University of Science, Vietnam National University, Ho Chi Minh City, Vietnam

    Phuc Van Pham & Ngoc Kim Phan

Authors
  1. Phuc Van Pham
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ngoc Kim Phan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Phuc Van Pham .

Editor information

Editors and Affiliations

  1. Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

    Kursad Turksen

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this protocol

Cite this protocol

Van Pham, P., Phan, N.K. (2014). Production of Good Manufacturing Practice-Grade Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells for Therapeutic Use. In: Turksen, K. (eds) Stem Cells and Good Manufacturing Practices. Methods in Molecular Biology, vol 1283. Humana Press, New York, NY. https://doi.org/10.1007/7651_2014_125

Download citation

  • DOI: https://doi.org/10.1007/7651_2014_125

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2434-9

  • Online ISBN: 978-1-4939-2435-6

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation