Skip to main content
SpringerLink
Log in

Review of biophysical factors affecting osteogenic differentiation of human adult adipose-derived stem cells

  • Review
  • Published:
Biophysical Reviews Aims and scope Submit manuscript

Abstract

Developing bone is subject to the control of a broad variety of influences in vivo. For bone repair applications, in vitro osteogenic assays are routinely used to test the responses of bone-forming cells to drugs, hormones, and biomaterials. Results of these assays are used to predict the behavior of bone-forming cells in vivo. Stem cell research has shown promise for enhancing bone repair. In vitro osteogenic assays to test the bone-forming response of stem cells typically use chemical solutions. Stem cell in vitro osteogenic assays often neglect important biophysical cues, such as the forces associated with regular weight-bearing exercise, which promote bone formation. Incorporating more biophysical cues that promote bone formation would improve in vitro osteogenic assays for stem cells. Improved in vitro osteogenic stimulation opens opportunities for “pre-conditioning” cells to differentiate towards the desired lineage. In this review, we explore the role of select biophysical factors—growth surfaces, tensile strain, fluid flow and electromagnetic stimulation—in promoting osteogenic differentiation of stem cells from human adipose. Emphasis is placed on the potential for physical microenvironment manipulation to translate tissue engineering and stem cell research into widespread clinical usage.

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
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Aksu AE, Rubin JP, Dudas JR, Marra KG (2008) Role of gender and anatomical region on induction of osteogenic differentiation of human adipose-derived stem cells. Ann Plast Surg 60(3):306–322

    Article  PubMed  CAS  Google Scholar 

  • Arnsdorf EJ, Tummala P, Jacobs CR (2009a) Non-canonical Wnt signaling and N-cadherin related beta-catenin signaling play a role in mechanically induced osteogenic cell fate. PLoS One 4(4):e5388

    Article  PubMed  Google Scholar 

  • Arnsdorf EJ, Tummala P, Kwon RY, Jacobs CR (2009b) Mechanically induced osteogenic differentiation–the role of RhoA, ROCKII and cytoskeletal dynamics. J Cell Sci 122(Pt 4):546–553

    Article  PubMed  CAS  Google Scholar 

  • Bodle JC, Hanson AD, Loboa EG (2011) Adipose-derived stem cells in functional bone tissue engineering: lessons from bone mechanobiology. Tissue Eng Part B Rev 17(3):195–211

    Article  PubMed  Google Scholar 

  • Burg KJPS, Kellam JF (2000) Biomaterial developments for bone tissue engineering. Biomaterials 21(23):2347–2359

    Article  PubMed  CAS  Google Scholar 

  • Calori GM, Mazza E, Colombo M, Ripamonti C (2011) The use of bone-graft substitutes in large bone defects: any specific needs? Injury 42(Suppl 2):S56–S63

    Article  PubMed  Google Scholar 

  • Casteilla L, Planat-Benard V, Laharrague P, Cousin B (2011) Adipose-derived stromal cells: their identity and uses in clinical trials, an update. World J Stem Cells 3(4):25–33

    Article  PubMed  Google Scholar 

  • Chou SY, Cheng CM, LeDuc PR (2009) Composite polymer systems with control of local substrate elasticity and their effect on cytoskeletal and morphological characteristics of adherent cells. Biomaterials 30(18):3136–3142

    Article  PubMed  CAS  Google Scholar 

  • Dulgar-Tulloch AJ, Bizios R, Siegel RW (2009) Human mesenchymal stem cell adhesion and proliferation in response to ceramic chemistry and nanoscale topography. J Biomed Mater Res A 90(2):586–594

    PubMed  CAS  Google Scholar 

  • Engler AJ, Sen S, Sweeney HL, Discher DE (2006) Matrix elasticity directs stem cell lineage specification. Cell 126(4):677–689

    Article  PubMed  CAS  Google Scholar 

  • Franceschi RT, Xiao G (2003) Regulation of the osteoblast-specific transcription factor, Runx2: responsiveness to multiple signal transduction pathways. J Cell Biochem 88(3):446–454

    Article  PubMed  CAS  Google Scholar 

  • Fröhlich MGW, Marolt D, Gimble JM, Kregar-Velikonja N, Vunjak-Novakovic G (2010) Bone grafts engineered from human adipose-derived stem cells in perfusion bioreactor culture. Tissue Eng Part A 16(1):179–189

    Article  PubMed  Google Scholar 

  • Frost H (1990) Skeletal structural adaptations to mechanical usage (SATMU): 1. Redefining Wolff's law: the bone modeling problem. Anat Rec 226(4):403–413

    Article  PubMed  CAS  Google Scholar 

  • Giardino et al. (2009) Electromagnetic field stimulator device for anatomic biophysical chondroprotection. U.S. Patent No. 7,566,295 B2, investors, Jul. 28

  • Gonzalez-Rey E, Gonzalez MA, Varela N, O'Valle F, Hernandez-Cortes P, Rico L, Büscher D, Delgado M (2010) Human adipose-derived mesenchymal stem cells reduce inflammatory and T cell responses and induce regulatory T cells in vitro in rheumatoid arthritis. Ann Rheum Dis 69(1):241–248

    Article  PubMed  CAS  Google Scholar 

  • Gorodetsky R, Levdansky L, Gaberman E, Gurevitch O, Lubzens E, McBride WH (2011) Fibrin microbeads loaded with mesenchymal cells support their long-term survival while sealed at room temperature. Tissue Eng Part C Methods 17(7):745–755

    Article  PubMed  CAS  Google Scholar 

  • Haimi S, Moimas L, Pirhonen E, Lindroos B, Huhtala H, Raty S, Kuokkanen H, Sandor GK, Miettinen S, Suuronen R (2009) Calcium phosphate surface treatment of bioactive glass causes a delay in early osteogenic differentiation of adipose stem cells. J Biomed Mater Res A 91(2):540–547

    PubMed  Google Scholar 

  • Hammerick KEJA, Huang Z, Prinz FB, Longaker MT (2010) Pulsed direct current electric fields enhance osteogenesis in adipose-derived stromal cells. Tissue Eng Part A 16(3):917–931

    Article  PubMed  CAS  Google Scholar 

  • Hanson AD, Marvel SW, Bernacki SH, Banes AJ, van Aalst J, Loboa EG (2009) Osteogenic effects of rest inserted and continuous cyclic tensile strain on hASC lines with disparate osteodifferentiation capabilities. Ann Biomed Eng 37(5):955–965

    Article  PubMed  Google Scholar 

  • Hao W, Pang L, Jiang M, Lv R, Xiong Z, Hu YY (2010) Skeletal repair in rabbits using a novel biomimetic composite based on adipose-derived stem cells encapsulated in collagen I gel with PLGA-beta-TCP scaffold. J Orthop Res 28(2):252–257

    PubMed  CAS  Google Scholar 

  • Hattori H, Masuoka K, Sato M, Ishihara M, Asazuma T, Takase B, Kikuchi M, Nemoto K (2006) Bone formation using human adipose tissue-derived stromal cells and a biodegradable scaffold. J Biomed Mater Res B Appl Biomater 76(1):230–239

    PubMed  Google Scholar 

  • He J, Genetos DC, Yellowley CE, Leach JK (2010) Oxygen tension differentially influences osteogenic differentiation of human adipose stem cells in 2D and 3D cultures. J Cell Biochem 110(1):87–96

    PubMed  CAS  Google Scholar 

  • Huang SC, Wu TC, Yu HC, Chen MR, Liu CM, Chiang WS, Lin KM (2010) Mechanical strain modulates age-related changes in the proliferation and differentiation of mouse adipose-derived stromal cells. BMC Cell Biol 11:18–31

    Article  PubMed  Google Scholar 

  • Jaalouk DE, Lammerding J (2009) Mechanotransduction gone awry. Nat Rev Mol Cell Biol 10(1):63–73

    Article  PubMed  CAS  Google Scholar 

  • Jessop HLRS, Pitsillides AA, Lanyon LE (2002) Mechanical strain and fluid movement both activate extracellular regulated kinase (ERK) in osteoblast-like cells but via different signaling pathways. Bone 31(1):186–194

    Article  PubMed  CAS  Google Scholar 

  • Joshi SD, Webb K (2008) Variation of cyclic strain parameters regulates development of elastic modulus in fibroblast/substrate constructs. J Orthop Res 26(8):1105–1113

    Article  PubMed  Google Scholar 

  • Kakudo N, Shimotsuma A, Miyake S, Kushida S, Kusumoto K (2008) Bone tissue engineering using human adipose-derived stem cells and honeycomb collagen scaffold. J Biomed Mater Res A 84(1):191–197

    PubMed  Google Scholar 

  • Kearney EM, Farrell E, Prendergast PJ, Campbell VA (2010) Tensile strain as a regulator of mesenchymal stem cell osteogenesis. Ann Biomed Eng 38(5):1767–1779

    Article  PubMed  CAS  Google Scholar 

  • Kim B-S, Park I-K, Hoshiba T, Jiang H-L, Choi Y-J, Akaike T, Cho C-S (2011) Design of artificial extracellular matrices for tissue engineering. Prog Polym Sci 36(2):238–268

    Article  CAS  Google Scholar 

  • Kroeze RJ, Knippenberg M, Helder MN (2011) Osteogenic differentiation strategies for adipose-derived mesenchymal stem cells. Methods Mol Biol 702:233–248

    Article  PubMed  CAS  Google Scholar 

  • Lendeckel S, Jödicke A, Christophis P, Heidinger K, Wolff J, Fraser JK, Hedrick MH, Berthold L, Howaldt HP (2004) Autologous stem cells (adipose) and fibrin glue used to treat widespread traumatic calvarial defects: case report. J Craniomaxillofac Surg 32(6):370–373

    Article  PubMed  Google Scholar 

  • Levi B, Longaker MT (2011) Concise review: adipose-derived stromal cells for skeletal regenerative medicine. Stem Cells 29(4):576–582

    Article  PubMed  CAS  Google Scholar 

  • Lindroos B, Aho KL, Kuokkanen H, Raty S, Huhtala H, Lemponen R, Yli-Harja O, Suuronen R, Miettinen S (2010) Differential gene expression in adipose stem cells cultured in allogeneic human serum versus fetal bovine serum. Tissue Eng Part A 16(7):2281–2294

    Article  PubMed  CAS  Google Scholar 

  • Liu L, Yuan W, Wang J (2010) Mechanisms for osteogenic differentiation of human mesenchymal stem cells induced by fluid shear stress. Biomech Model Mechanobiol 9(6):659–670

    Article  PubMed  Google Scholar 

  • Liu Q, Cen L, Yin S, Chen L, Liu G, Chang J, Cui L (2008) A comparative study of proliferation and osteogenic differentiation of adipose-derived stem cells on akermanite and beta-TCP ceramics. Biomaterials 29(36):4792–4799

    Article  PubMed  CAS  Google Scholar 

  • Lu Z, Roohani-Esfahani SI, Kwok PC, Zreiqat H (2011) Osteoblasts on rod shaped hydroxyapatite nanoparticles incorporated PCL film provide an optimal osteogenic niche for stem cell differentiation. Tissue Eng Part A 17(11–12):1651–1661

    Article  PubMed  CAS  Google Scholar 

  • Lund P, Pilgaard L, Duroux M, Fink T, Zachar V (2009) Effect of growth media and serum replacements on the proliferation and differentiation of adipose-derived stem cells. Cytotherapy 11(2):189–197

    Article  PubMed  CAS  Google Scholar 

  • Luu YK, Capilla E, Rosen CJ, Gilsanz V, Pessin JE, Judex S, Rubin CT (2009) Mechanical stimulation of mesenchymal stem cell proliferation and differentiation promotes osteogenesis while preventing dietary-induced obesity. J Bone Miner Res 24(1):50–61

    Article  PubMed  CAS  Google Scholar 

  • Marino G, Rosso F, Cafiero G, Tortora C, Moraci M, Barbarisi M, Barbarisi A (2010) Beta-tricalcium phosphate 3D scaffold promote alone osteogenic differentiation of human adipose stem cells: in vitro study. J Mater Sci Mater Med 21(1):353–363

    Article  PubMed  CAS  Google Scholar 

  • McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS (2004) Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell 6(4):483–495

    Article  PubMed  CAS  Google Scholar 

  • McCullen SD, Haslauer CM, Loboa EG (2010a) Musculoskeletal mechanobiology: interpretation by external force and engineered substratum. J Biomech 43(1):119–127

    Article  PubMed  Google Scholar 

  • McCullen SD, McQuilling JP, Grossfeld RM, Lubischer JL, Clarke LI, Loboa EG (2010b) Application of low-frequency alternating current electric fields via interdigitated electrodes: effects on cellular viability, cytoplasmic calcium, and osteogenic differentiation of human adipose-derived stem cells. Tissue Eng Part C Methods 16(6):1377–1386

    Article  PubMed  CAS  Google Scholar 

  • Mesimäki K, Lindroos B, Törnwall J, Mauno J, Lindqvist C, Kontio R, Miettinen S, Suuronen R (2009) Novel maxillary reconstruction with ectopic bone formation by GMP adipose stem cells. Int J Oral Maxillofac Surg 38(3):201–209

    Article  PubMed  Google Scholar 

  • Nandi SKRS, Mukherjee P, Kundu B, De DK, Basu D (2010) Orthopaedic applications of bone graft & graft substitutes. Indian J Med Res 132:15–30

    PubMed  CAS  Google Scholar 

  • Quarto N, Behr B, Longaker MT (2010) Opposite spectrum of activity of canonical Wnt signaling in the osteogenic context of undifferentiated and differentiated mesenchymal cells: implications for tissue engineering. Tissue Eng Part A 16(10):3185–3197

    Article  PubMed  CAS  Google Scholar 

  • Ra JC, Kang SK, Shin IS, Park HG, Joo SA, Kim JG, Kang BC, Lee YS, Nakama K, Piao M, Sohl B, Kurtz A (2011) Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells. J Transl Med 21(9):181–191

    Google Scholar 

  • Reed CR, Han L, Andrady A, Caballero M, Jack MC, Collins JB, Saba SC, Loboa EG, Cairns BA, van Aalst JA (2009) Composite tissue engineering on polycaprolactone nanofiber scaffolds. Ann Plast Surg 62(5):505–512

    Article  PubMed  CAS  Google Scholar 

  • Rose R, Bryan-Frankson B (2008) Is there still a role for pulsed electromagnetic field in the treatment of delayed unions and nonunions? Internet J Orthop Surg 10(1)

  • Rubin J, Rubin C, Jacobs CR (2006) Molecular pathways mediating mechanical signaling in bone. Gene 367:1–16

    Article  PubMed  CAS  Google Scholar 

  • Scherberich A, Muller AM, Schäfer DJ, Banfi A, Martin I (2010) Adipose tissue-derived progenitors for engineering osteogenic and vasculogenic grafts. J Cell Physiol 225(2):348–3

    Article  PubMed  CAS  Google Scholar 

  • Sefcik LS, Neal RA, Kaszuba SN, Parker AM, Katz AJ, Ogle RC, Botchwey EA (2008) Collagen nanofibres are a biomimetic substrate for the serum-free osteogenic differentiation of human adipose stem cells. J Tissue Eng Regen Med 2(4):210–220

    Article  PubMed  CAS  Google Scholar 

  • Shoji T, Ii M, Mifune Y, Matsumoto T, Kawamoto A, Kwon SM, Kuroda T, Kuroda R, Kurosaka M, Asahara T (2010) Local transplantation of human multipotent adipose-derived stem cells accelerates fracture healing via enhanced osteogenesis and angiogenesis. Lab Invest 90(4):637–649

    Article  PubMed  Google Scholar 

  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676

    Article  PubMed  CAS  Google Scholar 

  • Teo BKAS, Chan LY, Yim EK (2010) Nanotopography/mechanical induction of stem-cell differentiation. Meth Cell Biol 98:241–294

    Article  Google Scholar 

  • Tepper et al., inventors; 2005 Jan. 13. Combined tissue/bone growth stimulator and external fixation device. U.S. Patent 6,678,562 B1.

  • Titushkin I, Cho M (2007) Modulation of cellular mechanics during osteogenic differentiation of human mesenchymal stem cells. Biophys J 93(10):3693–3702

    Article  PubMed  CAS  Google Scholar 

  • Tjabringa GS, Vezeridis PS, Zandieh-Doulabi B, Helder MN, Wuisman PI, Klein-Nulend J (2006) Polyamines modulate nitric oxide production and COX-2 gene expression in response to mechanical loading in human adipose tissue-derived mesenchymal stem cells. Stem Cells 24(10):2262–2269

    Article  PubMed  CAS  Google Scholar 

  • Tokuzawa Y, Yagi K, Yamashita Y, Nakachi Y, Nikaido I, Bono H, Ninomiya Y, Kanesaki-Yatsuka Y, Akita M, Motegi H, Wakana S, Noda T, Sablitzky F, Arai S, Kurokawa R, Fukuda T, Katagiri T, Schönbach C, Suda T, Mizuno Y, Okazaki Y (2010) Id4, a new candidate gene for senile osteoporosis, acts as a molecular switch promoting osteoblast differentiation. PLoS Genetics 6(7):e1001019 1–15

    Article  Google Scholar 

  • Wall ME, Rachlin A, Otey CA, Loboa EG (2007) Human adipose-derived adult stem cells upregulate palladin during osteogenesis and in response to cyclic tensile strain. Am J Physiol Cell Physiol 293(5):C1532–C1538

    Article  PubMed  CAS  Google Scholar 

  • Wells RG, Discher DE (2008) Matrix elasticity, cytoskeletal tension, and TGF-beta: the insoluble and soluble meet. Sci Signal 1(10):pe13 1–3

    Article  Google Scholar 

Download references

Acknowledgements

This review was completed with the support of the Global 30 Project for Establishing Core Universities for Internationalization of The Ministry of Education, Culture, Sports, Science and Technology of Japan, at the University of Tsukuba. I thank Nina Salazar, Professors Damien Hall, Michael Raghunath and Evelyn Yim for critical comments on this review. I also thank Kenichi Kimura and Trinh Nhu Thuy for their helpful introduction and discussions regarding adipose tissue stem cell biology.

Author information

Authors and Affiliations

  1. The University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Japan, 305-8575

    Georgina To’a Salazar & Osamu Ohneda

Authors
  1. Georgina To’a Salazar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Osamu Ohneda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Georgina To’a Salazar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Salazar, G.T., Ohneda, O. Review of biophysical factors affecting osteogenic differentiation of human adult adipose-derived stem cells. Biophys Rev 5, 11–28 (2013). https://doi.org/10.1007/s12551-012-0079-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12551-012-0079-6

Keywords

Search

Navigation