Skip to main content

Advertisement

SpringerLink
Log in

Efficacy and safety of human adipose tissue-derived mesenchymal stem cells for supporting hematopoiesis

  • Original Article
  • Published:
International Journal of Hematology Aims and scope Submit manuscript

Abstract

We have demonstrated that adipose tissue-derived mesenchymal stem cells (ADSCs) from mice are capable of reconstituting the hematopoietic microenvironment, and facilitate hematopoiesis more effectively than bone marrow-derived mesenchymal stem cells (BMSCs) in mouse. The ready accessibility of fat tissue rich in MSCs and the higher hematopoiesis-supporting capacities of ADSCs suggest that ADSCs might represent a new therapeutic modality for the regeneration of impaired hematopoiesis. As a further step towards their use in clinical practice, we established human BMSCs and ADSCs from healthy volunteers of similar age, and compared their proliferation capacities, hematopoiesis-supporting properties, and safety. In vitro cell proliferation studies revealed that ADSCs have a higher population doubling number than BMSCs. In vitro co-culture assays showed that ADSCs not only support human CD34+ peripheral blood stem cells (PBSCs), but also yield significantly more non-adherent hematic cells than BMSCs. In vitro progenitor assays revealed that ADSCs promote a higher frequency of early progenitors than do BMSCs. Interestingly, BM cellularity in irradiated mice that had received ADSCs tended to be higher than that of mice treated with BMSCs. When MSCs were injected into the BM cavity of tibiae, we observed no evidence of MSC-induced toxicity either during or after treatment. In addition, no microscopic abnormalities were observed in the bone marrow and major organs.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Weissman IL. Stem cells: units of development, units of regeneration, and units in evolution. Cell. 2000;100(1):157–68.

    Article  PubMed  CAS  Google Scholar 

  2. Scopes J, Bagnara M, Gordon-Smith EC, Ball SE, Gibson FM. Haemopoietic progenitor cells are reduced in aplastic anaemia. Br J Haematol. 1994;86(2):427–30.

    Article  PubMed  CAS  Google Scholar 

  3. Nakayama T, Mutsuga N, Tosato G. Effect of fibroblast growth factor 2 on stromal cell-derived factor 1 production by bone marrow stromal cells and hematopoiesis. J Natl Cancer Inst. 2007;99(3):223–35.

    Article  PubMed  CAS  Google Scholar 

  4. Carlo-Stella C, Tabilio A, Regazzi E, Garau D, La Tagliata R, Trasarti S, Andrizzi C, Vignetti M, Meloni G. Effect of chemotherapy for acute myelogenous leukemia on hematopoietic and fibroblast marrow progenitors. Bone Marrow Transplant. 1997;20(6):465–71.

    Article  PubMed  CAS  Google Scholar 

  5. Kemp K, Morse R, Wexler S, Cox C, Mallam E, Hows J, Donaldson C. Chemotherapy-induced mesenchymal stem cell damage in patients with hematological malignancy. Ann Hematol. 2010;89(7):701–13.

    Article  PubMed  CAS  Google Scholar 

  6. Naveiras O, Nardi V, Wenzel PL, Hauschka PV, Fahey F, Daley GQ. Bone-marrow adipocytes as negative regulators of the haematopoietic microenvironment. Nature. 2009;460(7252):259–63.

    Article  PubMed  CAS  Google Scholar 

  7. Muguruma Y, Yahata T, Miyatake H, Sato T, Uno T, Itoh J, Kato S, Ito M, Hotta T, Ando K. Reconstitution of the functional human hematopoietic microenvironment derived from human mesenchymal stem cells in the murine bone marrow compartment. Blood. 2006;107(5):1878–87.

    Article  PubMed  CAS  Google Scholar 

  8. in ‘t Anker PS, Noort WA, Kruisselbrink AB, Scherjon SA, Beekhuizen W, Willemze R, Kanhai HH, Fibbe WE. Nonexpanded primary lung and bone marrow-derived mesenchymal cells promote the engraftment of umbilical cord blood-derived CD34(+) cells in NOD/SCID mice. Exp Hematol. 2003;31(10):881–9.

  9. Nauta AJ, Westerhuis G, Kruisselbrink AB, Lurvink EG, Willemze R, Fibbe WE. Donor-derived mesenchymal stem cells are immunogenic in an allogeneic host and stimulate donor graft rejection in a nonmyeloablative setting. Blood. 2006;108(6):2114–20.

    Article  PubMed  CAS  Google Scholar 

  10. Nishida S, Endo N, Yamagiwa H, Tanizawa T, Takahashi HE. Number of osteoprogenitor cells in human bone marrow markedly decreases after skeletal maturation. J Bone Miner Metab. 1999;17(3):171–7.

    Article  PubMed  CAS  Google Scholar 

  11. Mueller SM, 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(4):583–90.

    Article  PubMed  CAS  Google Scholar 

  12. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7(2):211–28.

    Article  PubMed  CAS  Google Scholar 

  13. Nakao N, Nakayama T, Yahata T, Muguruma Y, Saito S, Miyata Y, Yamamoto K, Naoe T. Adipose tissue-derived mesenchymal stem cells facilitate hematopoiesis in vitro and in vivo. Advantages over bone marrow-derived mesenchymal stem cells. Am J Pathol. 2010;177(2):547–54.

    Article  PubMed  Google Scholar 

  14. Nakagami H, Maeda K, Morishita R, Iguchi S, Nishikawa T, Takami Y, Kikuchi Y, Saito Y, Tamai K, Ogihara T, Kaneda Y. Novel autologous cell therapy in ischemic limb disease through growth factor secretion by cultured adipose tissue-derived stromal cells. Arterioscler Thromb Vasc Biol. 2005;25(12):2542–7.

    Article  PubMed  CAS  Google Scholar 

  15. Rigotti G, Marchi A, Sbarbati A. Adipose-derived mesenchymal stem cells: past, present, and future. Aesthetic Plast Surg. 2009;33(3):271–3.

    Article  PubMed  Google Scholar 

  16. Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood. 2006;108(8):2509–19.

    Article  PubMed  CAS  Google Scholar 

  17. Puissant B, Barreau C, Bourin P, Clavel C, Corre J, Bousquet C, Taureau C, Cousin B, Abbal M, Laharrague P, Penicaud L, Casteilla L, Blancher A. Immunomodulatory effect of human adipose tissue-derived adult stem cells: comparison with bone marrow mesenchymal stem cells. Br J Haematol. 2005;129(1):118–29.

    Article  PubMed  Google Scholar 

  18. Yanez R, Lamana ML, Garcia-Castro J, Colmenero I, Ramirez M, Bueren JA. Adipose tissue-derived mesenchymal stem cells have in vivo immunosuppressive properties applicable for the control of the graft-versus-host disease. Stem Cells. 2006;24(11):2582–91.

    Article  PubMed  CAS  Google Scholar 

  19. Han J, Koh YJ, Moon HR, Ryoo HG, Cho CH, Kim I, Koh GY. Adipose tissue is an extramedullary reservoir for functional hematopoietic stem and progenitor cells. Blood. 2010;115(5):957–64.

    Article  PubMed  CAS  Google Scholar 

  20. Kern 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(5):1294–301.

    Article  PubMed  CAS  Google Scholar 

  21. Meuleman N, Tondreau T, Ahmad I, Kwan J, Crokaert F, Delforge A, Dorval C, Martiat P, Lewalle P, Lagneaux L, Bron D. Infusion of mesenchymal stromal cells can aid hematopoietic recovery following allogeneic hematopoietic stem cell myeloablative transplant: a pilot study. Stem Cells Dev. 2009;18(9):1247–52.

    Article  PubMed  Google Scholar 

  22. Satoh H, Uesugi Y, Kawabata T, Mori K, Fujii F, Kashimoto Y, Kajimura T, Furuhama K. Morphological classification of dental lesions induced by various antitumor drugs in mice. Toxicol Pathol. 2001;29(3):292–9.

    Article  PubMed  CAS  Google Scholar 

  23. Rubio D, Garcia-Castro J, Martin MC, de la Fuente R, Cigudosa JC, Lloyd AC, Bernad A. Spontaneous human adult stem cell transformation. Cancer Res. 2005;65(8):3035–9.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Ms. Tomoko Kawake and Ms. Chika Wakamatsu for their technical assistance. This work was Grant Funding: Supported in part by the Japan Leukaemia Research Fund Grant to S.N. and, in part, by a Japanese Grant-in-Aid for Scientific Research [(C) 20591118] to T.N.

Author information

Author notes

  1. Takayuki Nakayama

    Present address: Department of Transfusion Medicine, Aichi Medical University, 21 Karimata, Yazako, Nagakute, Aichi, 480-1195, Japan

Authors and Affiliations

  1. Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan

    Satoshi Nishiwaki, Takayuki Nakayama, Shigeki Saito, Hiroki Mizuno, Tetsuya Nishida, Makoto Murata & Tomoki Naoe

  2. Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan

    Takenori Ozaki & Shoichi Maruyama

  3. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8550, Japan

    Yoshiyuki Takahashi & Seiji Kojima

Authors
  1. Satoshi Nishiwaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Takayuki Nakayama
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shigeki Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiroki Mizuno
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Takenori Ozaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yoshiyuki Takahashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shoichi Maruyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tetsuya Nishida
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Makoto Murata
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Seiji Kojima
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Tomoki Naoe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Takayuki Nakayama.

About this article

Cite this article

Nishiwaki, S., Nakayama, T., Saito, S. et al. Efficacy and safety of human adipose tissue-derived mesenchymal stem cells for supporting hematopoiesis. Int J Hematol 96, 295–300 (2012). https://doi.org/10.1007/s12185-012-1140-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12185-012-1140-8

Keywords

Search

Navigation