Abstract
Low-intensity pulsed ultrasound (LIPUS) stimulated the viability, proliferation and differentiation of hematopoietic stem/progenitor cells (HSPC) from fresh and cryopreserved peripheral blood leukapheresis product, as well as cord blood when applied for 10 min each day for 4 days. Cell viability, proliferation and differentiation were assessed on day 5 by viable cell counting, MTS proliferation assay, flow cytometry, and colony-forming unit assay. LIPUS stimulation: (i) enhanced the proliferation of fresh HSPC and maintained the viability of cryopreserved HSPC in vitro; (ii) did not affect the percentage of CD34+ and CD14+ cells; and (iii) enhanced burst-forming unit-erythroid colony formation. Hence, we suggest that this novel LIPUS stimulation approach might enhance the efficacy of clinical transplantation and cellular therapies using HSPC.
Similar content being viewed by others
References
Ang WT, Hoy W, El-Bialy T, Tsui YY, Chen J (2010) Design and implementation of therapeutic ultrasound generating circuit for dental tissue formation and tooth-root healing. IEEE Trans Biomed Circuits Syst 4:1–13
Bensinger WI, DiPersio JF, McCarty JM (2009) Improving stem cell mobilization strategies: future directions. Bone Marrow Transpl 43:181–195
Bordignon S (2006) Stem-cell therapies for blood diseases. Nature 441:1100–1102
Brada SJ, de Wolf JT, Hendriks D, Louwes H, van den Berg E, Vellenga E (1998) Characterization of the erythropoiesis in myelodysplasia by means of ferrokinetic studies, in vitro erythroid colony formation and soluble transferrin receptor. Leukemia 12:340–345
Bradley MB, Cairo MS (2005) Cord blood immunology and stem cell transplantation. Hum Immunol 66:431–446
Choi WH, Choi BH, Min BH, Park SR (2011) Low-intensity ultrasound increased colony forming unit-fibroblasts of mesenchymal stem cells during primary culture. Tissue Eng C Methods 17:517–526
Conneally E, Cashman J, Petzer A, Eaves C (1997) Expansion in vitro of transplantable human cord b blood stem cells demonstrated using a quantitative assay of their lympho-myeloid repopulating activity in non-obese diabetic-scid/scid mice. Proc Natl Acad Sci USA 94:9836–9841
Copelan EA (2006) Hematopoietic stem-cell transplantation. N Engl J Med 354:1813–1826
Dahlberg A, Delaney C, Bernstein ID (2011) Ex vivo expansion of human hematopoietic stem and progenitor cells. Blood 117:6083–6090
Doan N, Reher P, Meghji S, Harris M (1999) In vitro effects of therapeutic ultrasound on cell proliferation, protein synthesis, and cytokine production by human fibroblasts, osteoblasts, and monocytes. J Oral Maxillofac Surg 57:409–419
El-Bialy T (2007) Therapeutic ultrasound applications in craniofacial growth, healing and tissue engineering. Rejuvenation Res 10:367–371
El-Bialy T, El-Shamy I, Graber TM (2004) Repair of orthodontically induced root resorption by ultrasound in humans. Am J Orthod Dentofac Orthop 126:186–193
Gluckman E, Ruggeri A, Volt F, Cunha R, Boudjedirn K, Rocha V (2011) Milestones in umbilical cord blood transplantation. Br J Haematol 154:441–447
Gul H, Marquez-Curtis LA, Jahroudi N, Lo J, Turner AR, Janowska-Wieczorek A (2009) Valproic acid increases CXCR4 expression in hematopoietic stem/progenitor cells by chromatin remodeling. Stem Cells Dev 18:831–838
Gul-Uludag H, Peng X, Marquez-Curtis LA, Xing J, Janowska-Wieczorek A, Chen J (2011) Cationic liposome-mediated CXCR4 gene delivery into hematopoietic stem/progenitor cells: implications for clinical transplantation and gene therapy. Stem Cells Dev (Epub ahead of print Dec 14)
Heckman JD, Ryaby JP, McCabe J, Frey JJ, Kilcoyne RF (1994) Acceleration of tibial fracture healing by non-invasive, low-intensity pulsed ultrasound. J Bone Jt Surg Am 76:26–34
Iwashina T, Mochida J, Miyazaki T, Watanabe T, Iwabuchi S, Ando K, Hotta T, Sakai D (2006) Low-intensity pulsed ultrasound stimulates cell proliferation and proteoglycan production in rabbit intervertebral discs cells cultured in alginate. Biomaterials 27:354–361
Kaushansky K (1998) Thrombopoietin and hematopoietic stem cell. Blood 92:1–3
Kobayashi Y, Sakai D, Iwashina T, Iwabuchi S, Mochidam J (2009) Low-intensity pulsed ultrasound stimulates cell proliferation, proteoglycan synthesis and expression of growth factor- related genes in human nucleus pulposus cell line. J Eur Cell Mater 17:15–22
Park MY, Kim J, Lee DW, Park JS, Cho KI, Cho HJ, Park MY (1999) A 100 V, 10 mA high-voltage driver ICs for field emission display applications. In: Proceedings of 1st IEEE Asia Pacific Conference of ASICs, vol 1, pp 380–383
Petzer AL, Zandstra PW, Piret JM, Eaves CJ (1996) Differential cytokine effects on primitive (CD34+ CD38−) human hematopoietic cells: novel responses to Flt3-ligand and thrombopoietin. J Exp Med 183:2551–2558
Praloran V, Klausman M, Naud MF, Harousseau JL (1989) Blood erythroid progenitors (CFU-E and BFU-E) in acute lymphoblastic leukemias. Blut 58:75–78
Rubin C, Bolander M, Ryaby JP, Hadjiargyrou M (2001) The use of low-intensity ultrasound to accelerate the healing of fractures. JBJS 89:259–270
Villaron EM, Almeida J, Lopez-Holgado N, Sanchez-Guijo FM, Alberca M, Blanco B, Sanchez-Abarca LI, Lopez O, Perez-Simon JA, San Miguel JF, del Cañizo MC (2007) In leukapheresis products from non-Hodgkin’s lymphoma patients, the immature hematopoietic progenitors show higher CD90 and CD34 antigenic expression. Tranfus Apher Sci 37:145–156
Wang WT, Ker MD, Chiang MC, Chen CH (2001) Level shifter for high-speed 1 V to 3.3 V interfaces in a 0.13 μm Cu-interconnection/low-k CMOS technology. In: Proceedings of International Symposium on VLSI Technology, Systems, and Applications, vol 1, pp 307–310
Xing JZ, Yang X, Xu P, Ang WT, and Chen J (2011) Ultrasound enhanced monoclonal antibody production. Ultrasound Med Biol (accepted with minor revision)
Yun JH, Roh EY, Shin S, Jung NH, Song EY, Lee DS, Han KS, Kim JS, Kim BJ, Jeon HW, Yoon KS (2009) Introducing pulsed low-intensity ultrasound to culturing human umbilical cord-derived mesenchymal stem cells. Biotechnol Lett 31:329–335
Zhou S, Schmelz A, Seufferlein T, Li Y, Zhao J, Bachem MG (2004) Molecular mechanism of low intensity pulsed ultrasound in human skin fibroblast. J Biol Chem 279:54463–54469
Acknowledgments
The authors would like to acknowledge funding support from the Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada, the Industrial Research Assistance Program of the National Research Council of Canada, and Canadian Blood Services (CBS)/CIHR Blood Utilization and Conservation Initiative (XE00025 to AJW). The authors would also like to acknowledge the valuable discussions and inputs of Dr. Tarek El-Bialy (Department of Dentistry, the University of Alberta, Edmonton, Alberta, Canada). We are grateful for the frozen leukapheresis products provided by Brenda Letcher, and for technical assistance of Maria Cabuhat (Stem Cell Group, CBS, Edmonton, Alberta, Canada). We thank Donna Dawson (Perinatal Research Centre, University of Alberta) for the fresh cord blood collections.
Author information
Authors and Affiliations
Corresponding author
Additional information
Peng Xu and Hilal Gul-Uludag contributed equally to this study.
Rights and permissions
About this article
Cite this article
Xu, P., Gul-Uludag, H., Ang, W.T. et al. Low-intensity pulsed ultrasound-mediated stimulation of hematopoietic stem/progenitor cell viability, proliferation and differentiation in vitro. Biotechnol Lett 34, 1965–1973 (2012). https://doi.org/10.1007/s10529-012-0984-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10529-012-0984-6