Produção Nacional
Revisado por pares
Mesenchymal stem cells from umbilical cord: Do not discard the cord!
2007; Elsevier BV; Volume: 18; Issue: 1 Linguagem: Inglês
10.1016/j.nmd.2007.11.003
ISSN1873-2364
AutoresMariane Secco, Eder Zucconi, Natássia M. Vieira, Luciana Luchesi Quintanilha Fogaça, Antonia Cerqueira, Maria Denise F. Carvalho, Tatiana Jazedje, Oswaldo Keith Okamoto, Alysson R. Muotri, Mayana Zatz,
Tópico(s)Congenital Anomalies and Fetal Surgery
ResumoOn 10th February 2007, English entrepreneur Sir Richard Branson, best known for his Virgin brand of over 360 companies, announced the establishment of a cord blood bank, the Virgin Health Bank, in London. What makes this bank different is a dual public–private approach. A fifth of the cord blood would be stored for private use for the child or a family member and the rest would be donated to the public part of the bank which will be accessible to anyone in the world who needs it, at no cost. Additionally, Branson has pledged to donate his 50% of proceeds from Virgin Health Bank to researchers investigating the potential of cord blood stem cells [[1]The umbilical cord blood banking Richard Branson's way. Lancet 2007;369:437.Google Scholar]. The idea for the dual bank emerged when he was visited by a senior director of the National Blood Center, asking for his support in a charitable role, because children were dying through lack of umbilical cord blood. Initially Sir Richard offered 3 million pounds to the National Health Service to help them increase their storage capacity for umbilical cord blood, but the center was not comfortable with accepting funds from private sources. So Sir Richard decided to set up a company to do the job. This is an initiative that should be applauded but we want to draw attention to a very important and urgent aspect. The routine procedure in umbilical cord banks has been to store the blood and discard other tissues, such as the cord and/or placenta, which is a much better source of mesenchymal stem cells than blood [[2]Secco M. Zucconi E. Vieira N.M. et al.Multipotent stem cells from umbilical cord: cord is richer than blood!.Stem Cells. 2007; https://doi.org/10.1634/stemcells.2007-0381Crossref PubMed Scopus (310) Google Scholar]. Umbilical cord blood is rich in haematopoietic stem cells [3Cohena Y. Nagler A. Hematopoietic stem-cell transplantation using umbilical cord blood.Leuk Lymphoma. 2003; 44: 1287-1299Crossref PubMed Scopus (56) Google Scholar, 4Ooi J. The efficacy of unrelated cord blood transplantation for adult myelodysplastic syndrome.Leuk Lymphoma. 2006; 47: 599-602Crossref PubMed Scopus (31) Google Scholar, 5Laughlin M.J. Barker J. Bamback B. et al.Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors.N Engl J Med. 2001; 344: 1815-1822Crossref PubMed Scopus (754) Google Scholar, 6Hayani A. Lampeter E. Viswanatha D. Morgan D. Salvi S.N. First report of autologous cord blood transplantation in the treatment of a child with leukemia.Pediatrics. 2007; 119: 296-300Crossref Scopus (54) Google Scholar]. However the successful isolation of mesenchymal stem cells, which are undifferentiated cells able to self-renew, with high proliferative capacity, from the cord blood is controversial [7Lee O.K. Kuo T.K. Chen W.M. Lee K.D. Hsieh S.L. Chen T.H. Isolation of multipotent mesenchymal stem cells from umbilical cord blood.Blood. 2004; 103: 1669-1675Crossref PubMed Scopus (1246) Google Scholar, 8Erices A. Conget P. Minguell J.J. Mesenchymal progenitor cells in human umbilical cord blood.Br J Haematol. 2000; 109: 235-242Crossref PubMed Scopus (1443) Google Scholar, 9Goodwin H.S. Bicknese A.R. Chien S.N. Bogucki B.D. Quinn C.O. Wall D.A. Multilineage differentiation activity by cells isolated from umbilical cord blood: expression of bone, fat and neural markers.Biol Blood Marrow Transplant. 2001; 7: 581-588Abstract Full Text Full Text PDF PubMed Scopus (388) Google Scholar, 10Bieback K. Kern S. Kluter H. Eichler H. Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood.Stem Cells. 2004; 22: 625-634Crossref PubMed Scopus (795) Google Scholar, 11Romanov Y.A. Svintsitskaya V.A. Smirnov V.N. Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord.Stem Cells. 2003; 21: 105-110Crossref PubMed Scopus (818) Google Scholar, 12Mareschi K. Biasin E. Piacibello W. Aglietta M. Madon E. Fagioli F. Isolation of human mesenchymal stem cells: bone marrow versus umbilical cord blood.Haematologica. 2001; 86: 1099-1100PubMed Google Scholar, 13Wexler S.A. Donaldson C. Denning-Kendall P. Rice C. Bradley B. Hows J.M. Adult bone marrow is a rich source of human mesenchymal 'stem' cells but umbilical cord and mobilized adult blood are not.Br J Haematol. 2003; 121: 368-374Crossref PubMed Scopus (612) Google Scholar]. These cells comprise a rare population of multipotent precursors that in addition to supporting haematopoiesis are able to differentiate into various cell types such as chondrocytes, osteocytes, adipocytes and myocytes [14Zuk P.A. Zhu M. Ashjian P. et al.Human adipose tissue is a source of multipotent stem cells.Mol Biol Cell. 2002; 13: 4279-4295Crossref PubMed Scopus (5620) Google Scholar, 15Gang E.J. Jeong J.A. Hong S.H. et al.Skeletal myogenic differentiation of mesenchymal stem cells isolated from human umbilical cord blood.Stem Cells. 2004; 22: 617-624Crossref PubMed Scopus (269) Google Scholar, 16Karahuseyinoglu S. Cinar O. Kilic E. et al.Biology of the stem cells in human umbilical cord stroma: in situ and in vitro surveys.Stem Cells. 2007; 25: 319-331Crossref PubMed Scopus (470) Google Scholar, 17Kern S. Eichler H. Stoeve J. Kluter H. Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue.Stem Cells. 2006; 24: 1294-1301Crossref PubMed Scopus (2634) Google Scholar]. Bone marrow has been considered as one of the main sources of mesenchymal stem cells for both experimental and clinical applications and most of the knowledge concerning these cells came from bone marrow studies. However, obtaining them is painful and yields a low number of cells [18Mueller S.M. Glowacki J. Age-related decline in the osteogenic potential of human bone marrow cells cultured in three-dimensional collagen sponges.J Cell Biochem. 2001; 82: 583-590Crossref PubMed Scopus (419) Google Scholar, 19Stenderup K. Justuesen J. Clausen C. Kassem M. Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells.Bone. 2003; 33: 919-926Abstract Full Text Full Text PDF PubMed Scopus (1015) Google Scholar]. More recently, human umbilical cord blood taken after full term delivery of the newborn, from a sample that would be inevitably discarded has been regarded as an alternative source for transplantation and therapy because of its haematopoietic and mesenchymal components. However, while some researchers succeeded in the isolation of mesenchymal stem cells from umbilical cord blood [7Lee O.K. Kuo T.K. Chen W.M. Lee K.D. Hsieh S.L. Chen T.H. Isolation of multipotent mesenchymal stem cells from umbilical cord blood.Blood. 2004; 103: 1669-1675Crossref PubMed Scopus (1246) Google Scholar, 8Erices A. Conget P. Minguell J.J. Mesenchymal progenitor cells in human umbilical cord blood.Br J Haematol. 2000; 109: 235-242Crossref PubMed Scopus (1443) Google Scholar, 9Goodwin H.S. Bicknese A.R. Chien S.N. Bogucki B.D. Quinn C.O. Wall D.A. Multilineage differentiation activity by cells isolated from umbilical cord blood: expression of bone, fat and neural markers.Biol Blood Marrow Transplant. 2001; 7: 581-588Abstract Full Text Full Text PDF PubMed Scopus (388) Google Scholar, 10Bieback K. Kern S. Kluter H. Eichler H. Critical parameters for the isolation of mesenchymal stem cells from umbilical cord blood.Stem Cells. 2004; 22: 625-634Crossref PubMed Scopus (795) Google Scholar] others failed or obtained low yield [11Romanov Y.A. Svintsitskaya V.A. Smirnov V.N. Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord.Stem Cells. 2003; 21: 105-110Crossref PubMed Scopus (818) Google Scholar, 12Mareschi K. Biasin E. Piacibello W. Aglietta M. Madon E. Fagioli F. Isolation of human mesenchymal stem cells: bone marrow versus umbilical cord blood.Haematologica. 2001; 86: 1099-1100PubMed Google Scholar, 13Wexler S.A. Donaldson C. Denning-Kendall P. Rice C. Bradley B. Hows J.M. Adult bone marrow is a rich source of human mesenchymal 'stem' cells but umbilical cord and mobilized adult blood are not.Br J Haematol. 2003; 121: 368-374Crossref PubMed Scopus (612) Google Scholar]. More recently, some groups have reported success in isolating and establishing mesenchymal stem cells cultures from umbilical cord vein and UC stroma, also called Wharton's jelly [11Romanov Y.A. Svintsitskaya V.A. Smirnov V.N. Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord.Stem Cells. 2003; 21: 105-110Crossref PubMed Scopus (818) Google Scholar, 16Karahuseyinoglu S. Cinar O. Kilic E. et al.Biology of the stem cells in human umbilical cord stroma: in situ and in vitro surveys.Stem Cells. 2007; 25: 319-331Crossref PubMed Scopus (470) Google Scholar, 20Wang H.S. Hung S.C. Peng S.T. et al.Mesenchymal stem cells in the Wharton's jelly of the human umbilical cord.Stem Cells. 2004; 22: 1330-1337Crossref PubMed Scopus (1154) Google Scholar, 21Sarugaser R. Lickorish D. Baksh D. Hosseini M. Davies J.E. Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors.Stem Cells. 2005; 23: 220-229Crossref PubMed Scopus (706) Google Scholar]. According to Tondreau et al. [[22]Tondreau T. Meuleman N. Delforge A. et al.Mesenchymal stem cells derived from CD133-positive cells in mobilized peripheral blood and cord blood: proliferation, Oct4 expression, and plasticity.Stem Cells. 2005; 23: 1105-1112Crossref PubMed Scopus (393) Google Scholar], these discrepant results might be explained by different isolation and culture methodologies. In order to address this question we compared, for the first time, the efficiency in obtaining mesenchymal stem cells from 10 match-paired umbilical cord units harvested from the same donors, where the blood and the cord were processed simultaneously and under the same culture conditions [[2]Secco M. Zucconi E. Vieira N.M. et al.Multipotent stem cells from umbilical cord: cord is richer than blood!.Stem Cells. 2007; https://doi.org/10.1634/stemcells.2007-0381Crossref PubMed Scopus (310) Google Scholar]. Mesenchymal stem cells from blood were obtained from only one among the 10 cord samples collected but we were able to generate large amounts of primary mesenchymal stem cells cultures from all cord samples, with a 100% yield, which showed that the low yield of these progenitor cells in umbilical cord blood is not due to different culture methodologies. These results are in accordance with our previous experience where we observed that the efficiency in isolating mesenchymal stem cells from approximately 100 umbilical cord blood units stands around 10% (unpublished data). These cells isolated by a fast and simple procedure using short enzymatic digestion, may be expanded in vitro, cryogenic stored and thawed [[2]Secco M. Zucconi E. Vieira N.M. et al.Multipotent stem cells from umbilical cord: cord is richer than blood!.Stem Cells. 2007; https://doi.org/10.1634/stemcells.2007-0381Crossref PubMed Scopus (310) Google Scholar]. Despite the advantages of umbilical cord blood in haematopoietic reconstitution [3Cohena Y. Nagler A. Hematopoietic stem-cell transplantation using umbilical cord blood.Leuk Lymphoma. 2003; 44: 1287-1299Crossref PubMed Scopus (56) Google Scholar, 4Ooi J. The efficacy of unrelated cord blood transplantation for adult myelodysplastic syndrome.Leuk Lymphoma. 2006; 47: 599-602Crossref PubMed Scopus (31) Google Scholar, 5Laughlin M.J. Barker J. Bamback B. et al.Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors.N Engl J Med. 2001; 344: 1815-1822Crossref PubMed Scopus (754) Google Scholar], results from our study demonstrated that the umbilical cord and not the blood is the best choice for isolating mesenchymal stem cells for future applications. Storing umbilical cord blood in private or public banks has been recently the subject of many ethical dilemmas. A great obstacle to the altruistic proposal of Sir Richard Branson to split umbilical cord blood samples in both private and public banks is that the number of cells from one umbilical cord blood unit is usually not sufficient for an adult weighing more than 50 kg, which is a main limiting factor. In short, the important take home message is that regardless of being public or private, these banks are discarding the umbilical cord, a precious source of mesenchymal stem cells. Therefore, we suggest storing both the blood and the umbilical cord, which would allow maximum recovery of hematopoietic and mesenchymal stem cells for possible therapeutic applications in the future. Moreover, the possibility of originating different cell lines obtained from umbilical cord of neonates with malformations or genetic disorders, in particular myogenic lineages from patients with mutations responsible for neuromuscular disorders, may open new avenues for research of vast interest in addition to speed up screening process for therapeutic drugs.
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