Skip to main content

Advertisement

SpringerLink
Log in

Musculoskeletal tissue engineering by endogenous stem/progenitor cells

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

From its inception, tissue engineering has had three tenets: cells, biomaterial scaffolds and signaling molecules. Among the triad, cells are the center piece, because cells are the building blocks of tissues. For decades, cell therapies have focused on the procurement, manipulation and delivery of healthy cells for the treatment of diseases or trauma. Given the complexity and potential high cost of cell delivery, there is recent and surging interest to orchestrate endogenous cells for tissue regeneration. Biomaterial scaffolds are vital for many but not all, tissue-engineering applications and serve to accommodate or promote multiple cellular functions. Signaling molecules can be produced by transplanted cells or endogenous cells, or delivered specifically to regulate cell functions. This review highlights recent work in tissue engineering and cell therapies, with a focus on harnessing the capacity of endogenous cells as an alternative or adjunctive approach for tissue regeneration.

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
Fig. 6

Similar content being viewed by others

References

  • Agrawal V, Johnson SA, Reing J, Zhang L, Tottey S, Wang G, Hirschi KK, Braunhut S, Gudas LJ, Badylak SF (2010) Epimorphic regeneration approach to tissue replacement in adult mammals. Proc Natl Acad Sci USA 107:3351–3355

    Article  PubMed  CAS  Google Scholar 

  • Atala A, Bauer SB, Soker S, Yoo JJ, Retik AB (2006) Tissue-engineered autologous bladders for patients needing cystoplasty. Lancet 367:1241–1246

    Article  PubMed  Google Scholar 

  • Barbash IM, Chouraqui P, Baron J, Feinberg MS, Etzion S, Tessone A, Miller L, Guetta E, Zipori D, Kedes LH, Kloner RA, Leor J (2003) Systemic delivery of bone marrow-derived mesenchymal stem cells to the infarcted myocardium: feasibility, cell migration, and body distribution. Circulation 108:863–868

    Article  PubMed  Google Scholar 

  • Belema-Bedada F, Uchida S, Martire A, Kostin S, Braun T (2008) Efficient homing of multipotent adult mesenchymal stem cells depends on FROUNT-mediated clustering of CCR2. Cell Stem Cell 2:566–575

    Article  PubMed  CAS  Google Scholar 

  • Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L (1994) Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 331:889–895

    Article  PubMed  CAS  Google Scholar 

  • Bruder SP, Fox BS (1999) Tissue engineering of bone. Cell based strategies. Clin Orthop Relat Res 367:S68-S83

    Article  PubMed  Google Scholar 

  • Chang C, Lauffenburger DA, Morales TI (2003) Motile chondrocytes from newborn calf: migration properties and synthesis of collagen II. Osteoarthritis Cartilage 11:603–612

    Article  PubMed  CAS  Google Scholar 

  • Chen J, Li Y, Wang L, Zhang Z, Lu D, Lu M, Chopp M (2001) Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 32:1005–1011

    Article  PubMed  CAS  Google Scholar 

  • De Coppi P, Bartsch G Jr, Siddiqui MM, Xu T, Santos CC, Perin L, Mostoslavsky G, Serre AC, Snyder EY, Yoo JJ, Furth ME, Soker S, Atala A (2007) Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol 25:100–106

    Article  PubMed  Google Scholar 

  • Dellavalle A, Sampaolesi M, Tonlorenzi R, Tagliafico E, Sacchetti B, Perani L, Innocenzi A, Galvez BG, Messina G, Morosetti R, Li S, Belicchi M, Peretti G, Chamberlain JS, Wright WE, Torrente Y, Ferrari S, Bianco P, Cossu G (2007) Pericytes of human skeletal muscle are myogenic precursors distinct from satellite cells. Nat Cell Biol 9:255–267

    Article  PubMed  CAS  Google Scholar 

  • El Tamer MK, Reis RL (2009) Progenitor and stem cells for bone and cartilage regeneration. J Tissue Eng Regen Med 3:327–337

    Article  PubMed  CAS  Google Scholar 

  • Fiedler J, Brill C, Blum WF, Brenner RE (2006) IGF-I and IGF-II stimulate directed cell migration of bone-marrow-derived human mesenchymal progenitor cells. Biochem Biophys Res Commun 345:1177–1183

    Article  PubMed  CAS  Google Scholar 

  • Fiedler J, Etzel N, Brenner RE (2004) To go or not to go: migration of human mesenchymal progenitor cells stimulated by isoforms of PDGF. J Cell Biochem 93:990–998

    Article  PubMed  CAS  Google Scholar 

  • Fiedler J, Leucht F, Waltenberger J, Dehio C, Brenner RE (2005) VEGF-A and PlGF-1 stimulate chemotactic migration of human mesenchymal progenitor cells. Biochem Biophys Res Commun 334:561–568

    Article  PubMed  CAS  Google Scholar 

  • Fiedler J, Roderer G, Gunther KP, Brenner RE (2002) BMP-2, BMP-4, and PDGF-bb stimulate chemotactic migration of primary human mesenchymal progenitor cells. J Cell Biochem 87:305–312

    Article  PubMed  CAS  Google Scholar 

  • Fodor WL (2003) Tissue engineering and cell based therapies, from the bench to the clinic: the potential to replace, repair and regenerate. Reprod Biol Endocrinol 1:102

    Article  PubMed  Google Scholar 

  • Fox JM, Chamberlain G, Ashton BA, Middleton J (2007) Recent advances into the understanding of mesenchymal stem cell trafficking. Br J Haematol 137:491–502

    Article  PubMed  CAS  Google Scholar 

  • Frenkel SR, Clancy RM, Ricci JL, Di Cesare PE, Rediske JJ, Abramson SB (1996) Effects of nitric oxide on chondrocyte migration, adhesion, and cytoskeletal assembly. Arthritis Rheum 39:1905–1912

    Article  PubMed  CAS  Google Scholar 

  • Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP (1968) Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues Transplantation 6:230–247

    CAS  Google Scholar 

  • Friedenstein AJ, Piatetzky S II, Petrakova KV (1966) Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol 16:381–390

    PubMed  CAS  Google Scholar 

  • Fujita T, Azuma Y, Fukuyama R, Hattori Y, Yoshida C, Koida M, Ogita K, Komori T (2004) Runx2 induces osteoblast and chondrocyte differentiation and enhances their migration by coupling with PI3K-Akt signaling. J Cell Biol 166:85–95

    Article  PubMed  CAS  Google Scholar 

  • Gao J, Dennis JE, Solchaga LA, Goldberg VM, Caplan AI (2002) Repair of osteochondral defect with tissue-engineered two-phase composite material of injectable calcium phosphate and hyaluronan sponge. Tissue Eng 8:827–837

    Article  PubMed  CAS  Google Scholar 

  • Giannoudis PV, Einhorn TA, Marsh D (2007a) Fracture healing: a harmony of optimal biology and optimal fixation? Injury 38(Suppl 4):S1–S2

    Google Scholar 

  • Giannoudis PV, Einhorn TA, Marsh D (2007b) Fracture healing: the diamond concept. Injury 38(Suppl 4):S3–S6

    Article  Google Scholar 

  • Giannoudis PV, Einhorn TA, Schmidmaier G, Marsh D (2008) The diamond concept–open questions. Injury 39(Suppl 2):S5–S8

    Article  PubMed  Google Scholar 

  • Gojo S, Gojo N, Takeda Y, Mori T, Abe H, Kyo S, Hata J, Umezawa A (2003) In vivo cardiovasculogenesis by direct injection of isolated adult mesenchymal stem cells. Exp Cell Res 288:51–59

    Article  PubMed  CAS  Google Scholar 

  • Gronthos S, Brahim J, Li W, Fisher LW, Cherman N, Boyde A, DenBesten P, Robey PG, Shi S (2002) Stem cell properties of human dental pulp stem cells. J Dent Res 81:531–535

    Article  PubMed  CAS  Google Scholar 

  • Guilak F, Butler DL, Goldstein SA (2001) Functional tissue engineering: the role of biomechanics in articular cartilage repair. Clin Orthop Relat Res. Oct;(391 Suppl):S295–305

  • Guilak F, Lott KE, Awad HA, Cao Q, Hicok KC, Fermor B, Gimble JM (2006) Clonal analysis of the differentiation potential of human adipose-derived adult stem cells. J Cell Physiol 206:229–237

    Article  PubMed  CAS  Google Scholar 

  • Hidaka C, Cheng C, Alexandre D, Bhargava M, Torzilli PA (2006) Maturational differences in superficial and deep zone articular chondrocytes. Cell Tissue Res 323:127–135

    Article  PubMed  CAS  Google Scholar 

  • Hofstetter CP, Schwarz EJ, Hess D, Widenfalk J, El Manira A, Prockop DJ, Olson L (2002) Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. Proc Natl Acad Sci USA 99:2199–2204

    Article  PubMed  CAS  Google Scholar 

  • Imitola J, Raddassi K, Park KI, Mueller FJ, Nieto M, Teng YD, Frenkel D, Li J, Sidman RL, Walsh CA, Snyder EY, Khoury SJ (2004) Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci USA 101:18117–18122

    Article  PubMed  CAS  Google Scholar 

  • Jackson KA, Majka SM, Wang H, Pocius J, Hartley CJ, Majesky MW, Entman ML, Michael LH, Hirschi KK, Goodell MA (2001) Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 107:1395–1402

    Article  PubMed  CAS  Google Scholar 

  • Jain RK, Au P, Tam J, Duda DG, Fukumura D (2005) Engineering vascularized tissue. Nat Biotechnol 23:821–823

    Article  PubMed  CAS  Google Scholar 

  • Jiang CC, Chiang H, Liao CJ, Lin YJ, Kuo TF, Shieh CS, Huang YY, Tuan RS (2007) Repair of porcine articular cartilage defect with a biphasic osteochondral composite. J Orthop Res 25:1277–1290

    Article  PubMed  CAS  Google Scholar 

  • Karp JM, Leng Teo GS (2009) Mesenchymal stem cell homing: the devil is in the details. Cell Stem Cell 4:206–216

    Article  PubMed  CAS  Google Scholar 

  • Kirilak Y, Pavlos NJ, Willers CR, Han R, Feng H, Xu J, Asokananthan N, Stewart GA, Henry P, Wood D, Zheng MH (2006) Fibrin sealant promotes migration and proliferation of human articular chondrocytes: possible involvement of thrombin and protease-activated receptors. Int J Mol Med 17:551–558

    PubMed  CAS  Google Scholar 

  • Koike H, Morishita R, Iguchi S, Aoki M, Matsumoto K, Nakamura T, Yokoyama C, Tanabe T, Ogihara T, Kaneda Y (2003) Enhanced angiogenesis and improvement of neuropathy by cotransfection of human hepatocyte growth factor and prostacyclin synthase gene. FASEB J 17:779–781

    PubMed  CAS  Google Scholar 

  • Kopen GC, Prockop DJ, Phinney DG (1999) Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci USA 96:10711–10716

    Article  PubMed  CAS  Google Scholar 

  • Laird DJ, von Andrian UH, Wagers AJ (2008) Stem cell trafficking in tissue development, growth, and disease. Cell 132:612–630

    Article  PubMed  CAS  Google Scholar 

  • Langer R, Vacanti JP (1993) Tissue engineering. Science 260:920–926

    Article  PubMed  CAS  Google Scholar 

  • Lee CH, Cook JL, Mendelson A, Moioli EK, Yao H, Mao JJ (2010a) Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study. Lancet 376:440–448

    Article  CAS  Google Scholar 

  • Lee CH, Shah B, Moioli EK, Mao JJ (2010b) CTGF directs fibroblast differentiation from human mesenchymal stem/stromal cells and defines connective tissue healing in a rodent injury model. J Clin Invest 120:3340–3349

    Article  CAS  Google Scholar 

  • Lee OK, Kuo TK, Chen WM, Lee KD, Hsieh SL, Chen TH (2004) Isolation of multipotent mesenchymal stem cells from umbilical cord blood. Blood 103:1669–1675

    Article  PubMed  CAS  Google Scholar 

  • Levenberg S, Rouwkema J, Macdonald M, Garfein ES, Kohane DS, Darland DC, Marini R, van Blitterswijk CA, Mulligan RC, D'Amore PA, Langer R (2005) Engineering vascularized skeletal muscle tissue. Nat Biotechnol 23:879–884

    Article  PubMed  CAS  Google Scholar 

  • Mahmood A, Lu D, Lu M, Chopp M (2003) Treatment of traumatic brain injury in adult rats with intravenous administration of human bone marrow stromal cells. Neurosurgery 53:697–702; discussion 702–693

    Article  PubMed  Google Scholar 

  • Maniwa S, Ochi M, Motomura T, Nishikori T, Chen J, Naora H (2001) Effects of hyaluronic acid and basic fibroblast growth factor on motility of chondrocytes and synovial cells in culture. Acta Orthop Scand 72:299–303

    Article  PubMed  CAS  Google Scholar 

  • Meng E, Guo Z, Wang H, Jin J, Wang J, Wu C, Wang L (2008) High mobility group box 1 protein inhibits the proliferation of human mesenchymal stem cells and promotes their migration and differentiation along osteoblastic pathway. Stem Cells Dev 17:805–813

    Article  PubMed  CAS  Google Scholar 

  • Mishima Y, Lotz M (2008) Chemotaxis of human articular chondrocytes and mesenchymal stem cells. J Orthop Res 26:1407–1412

    Article  PubMed  Google Scholar 

  • Nakashima M, Reddi AH (2003) The application of bone morphogenetic proteins to dental tissue engineering. Nat Biotechnol 21:1025–1032

    Article  PubMed  CAS  Google Scholar 

  • Noh MJ, Copeland RO, Yi Y, Choi KB, Meschter C, Hwang S, Lim CL, Yip V, Hyun JP, Lee HY, Lee KH (2010) Pre-clinical studies of retrovirally transduced human chondrocytes expressing transforming growth factor-beta-1 (TG-C). Cytotherapy 12:384–393

    Article  PubMed  CAS  Google Scholar 

  • Ortiz LA, Gambelli F, McBride C, Gaupp D, Baddoo M, Kaminski N, Phinney DG (2003) Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci USA 100:8407–8411

    Article  PubMed  CAS  Google Scholar 

  • Ott HC, Matthiesen TS, Goh SK, Black LD, Kren SM, Netoff TI, Taylor DA (2008) Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart. Nat Med 14:213–221

    Article  PubMed  CAS  Google Scholar 

  • Ozaki Y, Nishimura M, Sekiya K, Suehiro F, Kanawa M, Nikawa H, Hamada T, Kato Y (2007) Comprehensive analysis of chemotactic factors for bone marrow mesenchymal stem cells. Stem Cells Dev 16:119–129

    Article  PubMed  CAS  Google Scholar 

  • Pangarkar N, Pharoah M, Nigam A, Hutmacher DW, Champ S (2010) Advanced Tissue Sciences Inc.: learning from the past, a case study for regenerative medicine. Regen Med 5:823–835

    Article  PubMed  Google Scholar 

  • Pelttari K, Lorenz H, Boeuf S, Templin MF, Bischel O, Goetzke K, Hsu HY, Steck E, Richter W (2008) Secretion of matrix metalloproteinase 3 by expanded articular chondrocytes as a predictor of ectopic cartilage formation capacity in vivo. Arthritis Rheum 58:467–474

    Article  PubMed  CAS  Google Scholar 

  • Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  PubMed  CAS  Google Scholar 

  • Ponte AL, Marais E, Gallay N, Langonne A, Delorme B, Herault O, Charbord P, Domenech J (2007) The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities. Stem Cells 25:1737–1745

    Article  PubMed  CAS  Google Scholar 

  • Reddi AH (1998) Role of morphogenetic proteins in skeletal tissue engineering and regeneration. Nat Biotechnol 16:247–252

    Article  PubMed  CAS  Google Scholar 

  • Richardson TP, Peters MC, Ennett AB, Mooney DJ (2001) Polymeric system for dual growth factor delivery. Nat Biotechnol 19:1029–1034

    Article  PubMed  CAS  Google Scholar 

  • Richter W (2009) Mesenchymal stem cells and cartilage in situ regeneration. J Intern Med 266:390–405

    Article  PubMed  CAS  Google Scholar 

  • Robey PG (2011) Cell sources for bone regeneration: the good, the bad, and the ugly (but promising). Tissue Eng Part B Rev 17:423–430

    Article  PubMed  CAS  Google Scholar 

  • Scotti C, Tonnarelli B, Papadimitropoulos A, Scherberich A, Schaeren S, Schauerte A, Lopez-Rios J, Zeller R, Barbero A, Martin I (2010) Recapitulation of endochondral bone formation using human adult mesenchymal stem cells as a paradigm for developmental engineering. Proc Natl Acad Sci USA 107:7251–7256

    Article  PubMed  CAS  Google Scholar 

  • Seale P, Asakura A, Rudnicki MA (2001) The potential of muscle stem cells. Dev Cell 1:333–342

    Article  PubMed  CAS  Google Scholar 

  • Takebayashi T, Iwamoto M, Jikko A, Matsumura T, Enomoto-Iwamoto M, Myoukai F, Koyama E, Yamaai T, Matsumoto K, Nakamura T et al (1995) Hepatocyte growth factor/scatter factor modulates cell motility, proliferation, and proteoglycan synthesis of chondrocytes. J Cell Biol 129:1411–1419

    Article  PubMed  CAS  Google Scholar 

  • Uchida K, Urabe K, Naruse K, Ujihira M, Mabuchi K, Itoman M (2007) Comparison of the cytokine-induced migratory response between primary and subcultured populations of rat mesenchymal bone marrow cells. J Orthop Sci 12:484–492

    Article  PubMed  CAS  Google Scholar 

  • Urist MR, DeLange RJ, Finerman GA (1983) Bone cell differentiation and growth factors. Science 220:680–686

    Article  PubMed  CAS  Google Scholar 

  • Warnke PH, Springer IN, Wiltfang J, Acil Y, Eufinger H, Wehmoller M, Russo PA, Bolte H, Sherry E, Behrens E, Terheyden H (2004) Growth and transplantation of a custom vascularised bone graft in a man. Lancet 364:766–770

    Article  PubMed  CAS  Google Scholar 

  • Weissman IL (2002) Stem cells—scientific, medical, and political issues. N Engl J Med 346:1576–1579

    Article  PubMed  Google Scholar 

  • Weissman IL (2006) Medicine: politic stem cells. Nature 439:145–147

    Article  PubMed  CAS  Google Scholar 

  • Woodruff MA, Hutmacher DW (2010) The return of a forgotten polymer—polycaprolactone in the 21st century. Prog Poly Sci 35:1217–1256

    Article  CAS  Google Scholar 

  • Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13:4279–4295

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank Fen Guo and Jackie Melendez for technical and administrative assistance. Effort in the composition of this article is partially funded by NIH grants RC2DEDE020767, R01EB009663 and R01DE018248.

Author information

Authors and Affiliations

  1. Tissue Engineering and Regenerative Medicine Laboratory (TERML), Columbia University Medical Center, 630 W. 168 St. – PH7E, New York, NY, 10032, USA

    Hemin Nie, Chang Hun Lee, Jiali Tan, Chuanyong Lu, Avital Mendelson, Mo Chen, Mildred C. Embree, Kimi Kong, Bhranti Shah, Shuang Wang, Shoko Cho & Jeremy J. Mao

Authors
  1. Hemin Nie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chang Hun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jiali Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chuanyong Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Avital Mendelson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mo Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mildred C. Embree
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kimi Kong
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bhranti Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Shuang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Shoko Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jeremy J. Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeremy J. Mao.

Additional information

Guest Editors: Dietmar W. Hutmacher, Robert Guldberg and Georg Duda

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nie, H., Lee, C.H., Tan, J. et al. Musculoskeletal tissue engineering by endogenous stem/progenitor cells. Cell Tissue Res 347, 665–676 (2012). https://doi.org/10.1007/s00441-012-1339-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-012-1339-2

Keywords

Search

Navigation