Abstract
Cystic fibrosis (CF) is a life-threatening autosomal recessive multi-organ disorder with the mean incidence of 0.737 per 10,000 people worldwide. Despite many advances in therapy, patients fail to have a satisfactory quality of life. The end-stage lung disease still accounts for significant mortality and puts patients in the need of lung transplantation. Even though the disease is monogenic, the trials of topical gene transfer into airway epithelial cells have so far been disappointing. It is proven that stem cells can be differentiated into type II alveolar epithelial cells. Wharton’s jelly-derived mesenchymal stem cells (MSC) from non-CF carrier third-party donors could be an effective alternative to bone marrow or embryonic stem cells. The harvesting process is an easy and ethically uncontroversial procedure. The MSC cell should be applied through repetitive infusions due to rapid lung epithelial cell turnover. However, the low stem cell incorporation remains a problem. Pre-clinical studies imply that even 6–10 % of the wild-type cystic fibrosis transmembrane conductance regulator (CFTR) expression could be enough to restore chloride secretion. The route of administration, the optimal dose, as well as the intervals between infusions have yet to be determined. This review discusses the clinical potential of mesenchymal stem cell in CF patients.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aliotta JM, Passero M, Meharg J, Klinger J, Dooner MS, Pimentel J, Quesenberry PJ (2005) Stem cells and pulmonary metamorphosis: new concepts in repair and regeneration. J Cell Physiol 204(3):725–741
Boruczkowski D, Ołdak T, Czaplicka I, Murzyn I, Olkowicz A, Pawelec K, Balogh I, Géza V, Pirciog D, Stefan R, Soguero C, Kalwak K, Ussowicz M, Mielcarek M, Chybicka A, Drabko K, Kowalczyk J, Michalski P (2012) The collection and cultivation of umbilical cord derived cells for potential clinical use. Bone Marrow Transplant 47(Suppl 1):280–281
Bruscia EM, Price JE, Cheng EC, Weiner S, Caputo C, Ferreira EC, Egan ME, Krause DS (2006) Assessment of cystic fibrosis transmembrane conductance regulator (CFTR) activity in CFTR-null mice after bone marrow transplantation. Proc Natl Acad Sci U S A 103:2965–2970
Caimi PF, Reese J, Lee Z, Lazarus HM (2010) Emerging therapeutic approaches for multipotent mesenchymal stromal cells. Curr Opin Hematol 17(6):505–513
Conese M, Copreni E, Di Gioia S, De Rinaldis P, Fumarulo R (2003) Neutrophil recruitment and airway epithelial cell involvement in chronic cystic fibrosis lung disease. J Cyst Fibros 2(3):129–135
Coraux C, Nawrocki-Raby B, Hinnrasky J, Kileztky C, Gaillard D, Dani C, Puchelle E (2005) Embryonic stem cells generate airway epithelial tissue. Am J Respir Cell Mol Biol 32(2):87–92
Gilpin SE, Lung K, de Couto GT, Cypel M, Sato M, Singer LG, Keshavjee S, Waddell TK (2013) Bone marrow-derived progenitor cells in end-stage lung disease patients. BMC Pulm Med 13:48
Kleeberger W, Versmold A, Rothämel T, Glöckner S, Bredt M, Haverich A, Lehmann U, Kreipe H (2003) Increased chimerism of bronchial and alveolar epithelium in human lung allografts undergoing chronic injury. Am J Pathol 162(5):1487–1494
Leblond AL, Naud P, Forest V, Gourden C, Sagan C, Romefort B, Mathieu E, Delorme B, Collin C, Pagès JC, Sensebé L, Pitard B, Lemarchand P (2009) Developing cell therapy techniques for respiratory disease: intratracheal delivery of genetically engineered stem cells in a murine model of airway injury. Hum Gene Ther 20(11):1329–1343
Loebinger MR, Aguilar S, Janes SM (2008) Therapeutic potential of stem cells in lung disease: progress and pitfalls. Clin Sci 114(2):99–108
Loi R, Beckett T, Goncz KK, Suratt BT, Weiss DJ (2006) Limited restoration of cystic fibrosis lung epithelium in vivo with adult marrow derived cells. Am J Respir Crit Care Med 173:171–179
Love Z, Wang F, Dennis J, Awadallah A, Salem N, Lin Y, Weisenberger A, Majewski S, Gerson S, Lee Z (2007) Imaging of mesenchymal stem cell transplant by bioluminescence and PET. J Nucl Med 48:2011–2020
Lubamba B, Dhooghe B, Noel S, Leal T (2012) Cystic fibrosis: insight into CFTR pathophysiology and pharmacotherapy. Clin Biochem 45(15):1132–1144
Painter RG, Valentine VG, Lanson NA, Leidal K, Zhang Q, Lombard G, Thompson C, Viswanathan A, Nauseef WM, Wang G, Wang G (2006) CFTR expression in human neutrophils and the phagolysosomal chlorination defect in cystic fibrosis. Biochemistry 45(34):10260–10269
Paracchini V, Carbone A, Colombo F, Castellani S, Mazzucchelli S, Gioia SD, Degiorgio D, Seia M, Porretti L, Colombo C, Conese M (2012) Amniotic mesenchymal stem cells: a new source for hepatocyte-like cells and induction of CFTR expression by coculture with cystic fibrosis airway epithelial cells. J Biomed Biotechnol 2012:575471
Quon BS, Aitken ML (2012) Cystic fibrosis: what to expect now in the early adult years. Paediatr Respir Rev 13(4):206–214
Spencer H, Jaffe A (2004) The potential for stem cell therapy in cystic fibrosis. J R Soc Med 97(Suppl 44):52–56
Sueblinvong V, Loi R, Eisenhauer PL, Bernstein IM, Suratt BT, Spees JL, Weiss DJ (2008) Derivation of lung epithelium from human cord blood-derived mesenchymal stem cells. Am J Respir Crit Care Med 177(7):701–711
Suratt BT, Cool CD, Serls AE, Chen L, Varella-Garcia M, Shpall EJ, Brown KK, Worthen GS (2003) Human pulmonary chimerism after hematopoietic stem cell transplantation. Am J Respir Crit Care Med 168(3):318–322
Suzuki T, Kobayashi K, Tada Y, Suzuki Y, Wada I, Nakamura T, Omori K (2008) Regeneration of the trachea using a bioengineered scaffold with adipose-derived stem cells. Ann Otol Rhinol Laryngol 117(6):453–463
Wang G, Bunnell BA, Painter RG, Quiniones BC, Tom S, Lanson NA Jr, Spees JL, Bertucci D, Peister A, Weiss DJ, Valentine VG, Prockop DJ, Kolls JK (2005) Adult stem cells from bone marrow stroma differentiate into airway epithelial cells: potential therapy for cystic fibrosis. Proc Natl Acad Sci U S A 102(1):186–191
Wang Y, Sun Z, Qiu X, Li Y, Qin J, Han X (2009) Roles of Wnt/beta-catenin signaling in epithelial differentiation of mesenchymal stem cells. Biochem Biophys Res Commun 390(4):1309–1314
Yan X, Liu Y, Han Q, Jia M, Liao L, Qi M, Zhao RC (2007) Injured microenvironment directly guides the differentiation of engrafted flk-1(+) mesenchymal stem cell in lung. Exp Hematol 35:1466–1475
Acknowledgments
DB and DG contributed equally to this work.
Conflicts of Interest
The authors declare no conflicts of interest in relation to this article.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Boruczkowski, D., Gładysz, D., Demkow, U., Pawelec, K. (2014). The Potential of Wharton’s Jelly Derived Mesenchymal Stem Cells in Treating Patients with Cystic Fibrosis. In: Pokorski, M. (eds) Lung Cancer and Autoimmune Disorders. Advances in Experimental Medicine and Biology(), vol 833. Springer, Cham. https://doi.org/10.1007/5584_2014_17
Download citation
DOI: https://doi.org/10.1007/5584_2014_17
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-09751-0
Online ISBN: 978-3-319-09752-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)