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Characterization and Differentiation of Circulating Blood Mesenchymal Stem Cells and the Role of Phosphatidylinositol 3-Kinase in Modulating the Adhesion

  • Park, Yoon-Kyung (Dental Research Institute, Seoul National University) ;
  • Heo, Seong-Joo (Dental Research Institute and Prosthodontics, Seoul National University Dental Hospital, School of Dentistry, Seoul National University) ;
  • Koak, Jai-Young (Dental Research Institute and Prosthodontics, Seoul National University Dental Hospital, School of Dentistry, Seoul National University) ;
  • Park, Gang-Seok (Dental Research Institute and Prosthodontics, Seoul National University Dental Hospital, School of Dentistry, Seoul National University) ;
  • Cho, Tae-Jun (Department of Dental Regenerative Biotechnology, School of Dentistry, Seoul National University) ;
  • Kim, Seong-Kyun (Dental Research Institute and Prosthodontics, Seoul National University Dental Hospital, School of Dentistry, Seoul National University) ;
  • Cho, Jaejin (Department of Dental Regenerative Biotechnology, School of Dentistry, Seoul National University)
  • Received : 2018.12.18
  • Accepted : 2019.02.26
  • Published : 2019.07.31

Abstract

Bone marrow mesenchymal stem cells (BM MSCs) can differentiate into multi-lineage tissues. However, obtaining BM MSCs by aspiration is difficult and can be painful; therefore peripheral blood (PB) MSCs might provide an easier alternative for clinical applications. Here, we show that circulating PB MSCs proliferate as efficiently as BM MSCs in the presence of extracellular matrix (ECM) and that differentiation potential into osteoblast in vitro and in vivo. Both BM MSCs and PB MSCs developed into new bone when subcutaneously transplanted into immune-compromised mice using hydroxyapatite/tricalcium phosphate as a carrier. Furthermore, LY294002 and Wortmannin blocked mesenchymal stem cell attachment in a dose-dependent manner, suggesting a role of phosphatidylinositol 3-kinase in MSC attachment. Our data showed that the growth of PB MSCs could be regulated by interaction with the ECM and that these cells could differentiate into osteoblasts, suggesting their potential for clinical applications.

Keywords

Acknowledgement

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2018R1D1A1B07042333) and Institute for Information & communication Technology Promotion (IITP) grant funded by the Korean Government (860-20180051).

References

  1. Ullah I, Subbarao RB, Rho GJ. Human mesenchymal stem cells - current trends and future prospective. Biosci Rep 2015;35. pii: e00191 https://doi.org/10.1042/BSR20150025
  2. Perlin JR, Sporrij A, Zon LI. Blood on the tracks: hematopoietic stem cell-endothelial cell interactions in homing and engraftment. J Mol Med (Berl) 2017;95:809-819 https://doi.org/10.1007/s00109-017-1559-8
  3. Xie C, Yang Z, Suo Y, Chen Q, Wei D, Weng X, Gu Z, Wei X. Systemically infused mesenchymal stem cells show different homing profiles in healthy and tumor mouse models. Stem Cells Transl Med 2017;6:1120-1131 https://doi.org/10.1002/sctm.16-0204
  4. Chamberlain G, Fox J, Ashton B, Middleton J. Concise review: mesenchymal stem cells: their phenotype, differentiation capacity, immunological features, and potential for homing. Stem Cells 2007;25:2739-2749 https://doi.org/10.1634/stemcells.2007-0197
  5. Trounson A, McDonald C. Stem cell therapies in clinical trials: progress and challenges. Cell Stem Cell 2015;17:11-22 https://doi.org/10.1016/j.stem.2015.06.007
  6. Goldberg A, Mitchell K, Soans J, Kim L, Zaidi R. The use of mesenchymal stem cells for cartilage repair and regeneration: a systematic review. J Orthop Surg Res 2017;12:39 https://doi.org/10.1186/s13018-017-0534-y
  7. Liotta F, Annunziato F, Castellani S, Boddi M, Alterini B, Castellini G, Mazzanti B, Cosmi L, Acquafresca M, Bartalesi F, Dilaghi B, Dorigo W, Graziani G, Bartolozzi B, Bellandi G, Carli G, Bartoloni A, Fargion A, Fassio F, Fontanari P, Landini G, Lucente EAM, Michelagnoli S, Orsi Battaglini C, Panigada G, Pigozzi C, Querci V, Santarlasci V, Parronchi P, Troisi N, Baggiore C, Romagnani P, Mannucci E, Saccardi R, Pratesi C, Gensini G, Romagnani S, Maggi E. Therapeutic efficacy of autologous non-mobilized enriched circulating endothelial progenitors in patients with critical limb ischemia - the SCELTA trial. Circ J 2018;82:1688-1698 https://doi.org/10.1253/circj.CJ-17-0720
  8. Freitag J, Bates D, Boyd R, Shah K, Barnard A, Huguenin L, Tenen A. Mesenchymal stem cell therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy - a review. BMC Musculoskelet Disord 2016;17:230 https://doi.org/10.1186/s12891-016-1085-9
  9. Zheng RC, Park YK, Cho JJ, Kim SK, Heo SJ, Koak JY, Lee JH. Bone regeneration at dental implant sites with suspended stem cells. J Dent Res 2014;93:1005-1013 https://doi.org/10.1177/0022034514548706
  10. Romanov YA, Svintsitskaya VA, Smirnov VN. Searching for alternative sources of postnatal human mesenchymal stem cells: candidate MSC-like cells from umbilical cord. Stem Cells 2003;21:105-110 https://doi.org/10.1634/stemcells.21-1-105
  11. Fahy N, Alini M, Stoddart MJ. Mechanical stimulation of mesenchymal stem cells: implications for cartilage tissue engineering. J Orthop Res 2018;36:52-63
  12. Fadini GP, Ciciliot S, Albiero M. Concise review: perspectives and clinical implications of bone marrow and circulating stem cell defects in diabetes. Stem Cells 2017;35:106-116 https://doi.org/10.1002/stem.2445
  13. Pineault N, Abu-Khader A. Advances in umbilical cord blood stem cell expansion and clinical translation. Exp Hematol 2015;43:498-513 https://doi.org/10.1016/j.exphem.2015.04.011
  14. Zheng RC, Park YK, Kim SK, Cho J, Heo SJ, Koak JY, Lee SJ, Park JM, Lee JH, Kim JH. Bone regeneration of blood-derived stem cells within dental implants. J Dent Res 2015;94:1318-1325 https://doi.org/10.1177/0022034515590368
  15. Wexler SA, Donaldson C, Denning-Kendall P, Rice C, Bradley B, Hows JM. 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;121:368-374 https://doi.org/10.1046/j.1365-2141.2003.04284.x
  16. Hassan G, Kasem I, Soukkarieh C, Aljamali M. A simple method to isolate and expand human umbilical cord derived mesenchymal stem cells: using explant method and umbilical cord blood serum. Int J Stem Cells 2017;10:184-192 https://doi.org/10.15283/ijsc17028
  17. Ward PS, Thompson CB. Signaling in control of cell growth and metabolism. Cold Spring Harb Perspect Biol 2012;4:a006783
  18. Scanlon V, Soung do Y, Adapala NS, Morgan E, Hansen MF, Drissi H, Sanjay A. Role of Cbl-PI3K interaction during skeletal remodeling in a murine model of bone repair. PLoS One 2015;10:e0138194 https://doi.org/10.1371/journal.pone.0138194
  19. Fruman DA, Chiu H, Hopkins BD, Bagrodia S, Cantley LC, Abraham RT. The PI3K pathway in human disease. Cell 2017;170:605-635 https://doi.org/10.1016/j.cell.2017.07.029
  20. Huang CY, Hagar KL, Frost LE, Sun Y, Cheung HS. Effects of cyclic compressive loading on chondrogenesis of rabbit bone-marrow derived mesenchymal stem cells. Stem Cells 2004;22:313-323 https://doi.org/10.1634/stemcells.22-3-313
  21. Hidalgo-Bastida LA, Cartmell SH. Mesenchymal stem cells, osteoblasts and extracellular matrix proteins: enhancing cell adhesion and differentiation for bone tissue engineering. Tissue Eng Part B Rev 2010;16:405-412 https://doi.org/10.1089/ten.teb.2009.0714
  22. Tondreau T, Meuleman N, Delforge A, Dejeneffe M, Leroy R, Massy M, Mortier C, Bron D, Lagneaux L. Mesenchymal stem cells derived from CD133-positive cells in mobilized peripheral blood and cord blood: proliferation, Oct4 expression, and plasticity. Stem Cells 2005;23:1105-1112 https://doi.org/10.1634/stemcells.2004-0330
  23. He Q, Wan C, Li G. Concise review: multipotent mesenchymal stromal cells in blood. Stem Cells 2007;25:69-77 https://doi.org/10.1634/stemcells.2006-0335
  24. Khosla S, Westendorf JJ, Modder UI. Concise review: insights from normal bone remodeling and stem cell-based therapies for bone repair. Stem Cells 2010;28:2124-2128 https://doi.org/10.1002/stem.546
  25. Wu G, Pan M, Wang X, Wen J, Cao S, Li Z, Li Y, Qian C, Liu Z, Wu W, Zhu L, Guo J. Osteogenesis of peripheral blood mesenchymal stem cells in self assembling peptide nanofiber for healing critical size calvarial bony defect. Sci Rep 2015;5:16681 https://doi.org/10.1038/srep16681
  26. Lakkakorpi PT, Wesolowski G, Zimolo Z, Rodan GA, Rodan SB. Phosphatidylinositol 3-kinase association with the osteoclast cytoskeleton, and its involvement in osteoclast attachment and spreading. Exp Cell Res 1997;237:296-306 https://doi.org/10.1006/excr.1997.3797
  27. Kim NG, Gumbiner BM. Adhesion to fibronectin regulates Hippo signaling via the FAK-Src-PI3K pathway. J Cell Biol 2015;210:503-515 https://doi.org/10.1083/jcb.201501025
  28. Chen XD, Dusevich V, Feng JQ, Manolagas SC, Jilka RL. Extracellular matrix made by bone marrow cells facilitates expansion of marrow-derived mesenchymal progenitor cells and prevents their differentiation into osteoblasts. J Bone Miner Res 2007;22:1943-1956 https://doi.org/10.1359/jbmr.070725