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Published in: International Orthopaedics 5/2015

Open Access 01-05-2015 | Review Article

The role of growth factors in stem cell-directed chondrogenesis: a real hope for damaged cartilage regeneration

Authors: Ewelina Augustyniak, Tomasz Trzeciak, Magdalena Richter, Jacek Kaczmarczyk, Wiktoria Suchorska

Published in: International Orthopaedics | Issue 5/2015

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Abstract

Purpose

The use of stem cells in regenerative medicine offers hope to treat numerous orthopaedic disorders, including articular cartilage defects. Although much research has been carried out on chondrogenesis, this complicated process is still not well understood and much more research is needed. The present review provides an overview of the stages of chondrogenesis and describes the effects of various growth factors, which act during the multiple steps involved in stem cell-directed differentiation towards chondrocytes.

Methods

The current literature on stem cell-directed chondrogenesis, in particular the role of members of the transforming growth factor-β (TGF-β) superfamily—TGF-βs, bone morphogenetic proteins (BMPs) and fibroblast growth factors (FGFs)—is reviewed and discussed.

Results

Numerous studies have reported the chondrogenic potential of both adult- and embryonic-like stem cells and the role of growth factors in programming differentiation of these cells towards chondrocytes. Mesenchymal stem cells (MSCs) are adult multipotent stem cells, whereas induced pluripotent stem cells (iPSC) are reprogrammed pluripotent cells. Although better understanding of the processes involved in the development of cartilage tissues is necessary, both cell types may be of value in the clinical treatment of cartilage injuries or osteoarthritic cartilage lesions.

Conclusions

MSCs and iPSCs both present unique characteristics. However, at present, it is still unclear which cell type is most suitable in the treatment of cartilage injuries.
Literature
1.
go back to reference Cole BJ, Pascual-Garrido C, Grumet RC (2009) Surgical management of articular cartilage defects in the knee. J Bone Joint Surg Am 91:1778–1790PubMed Cole BJ, Pascual-Garrido C, Grumet RC (2009) Surgical management of articular cartilage defects in the knee. J Bone Joint Surg Am 91:1778–1790PubMed
2.
go back to reference Gomoll AH, Filardo G, de Girolamo L, Esprequeira-Mendes J, Marcacci M, Rodkey WG, Steadman RJ, Zaffagnini S, Kon E (2012) Surgical treatment for early osteoarthritis. Part I: cartilage repair procedures. Knee Surg Sports Traumatol Arthrosc 20:450–466. doi:10.1007/s00167-011-1780-x CrossRefPubMed Gomoll AH, Filardo G, de Girolamo L, Esprequeira-Mendes J, Marcacci M, Rodkey WG, Steadman RJ, Zaffagnini S, Kon E (2012) Surgical treatment for early osteoarthritis. Part I: cartilage repair procedures. Knee Surg Sports Traumatol Arthrosc 20:450–466. doi:10.​1007/​s00167-011-1780-x CrossRefPubMed
3.
go back to reference Kreuz PC, Steinwachs MR, Erggelet C, Krause SJ, Konrad G, Uhl M, Südkamp N (2006) Results after microfracture of full-thicness chondral defects in different compartments in the knee. Osteoarth Cart 14:1119–1125. doi:10.1016/j.joca.2006.05.003 CrossRef Kreuz PC, Steinwachs MR, Erggelet C, Krause SJ, Konrad G, Uhl M, Südkamp N (2006) Results after microfracture of full-thicness chondral defects in different compartments in the knee. Osteoarth Cart 14:1119–1125. doi:10.​1016/​j.​joca.​2006.​05.​003 CrossRef
4.
go back to reference Jones DG, Peterson L (2006) Autologous chondrocyte implantation. J Bone Joint Surg Am 88:2501–2520CrossRef Jones DG, Peterson L (2006) Autologous chondrocyte implantation. J Bone Joint Surg Am 88:2501–2520CrossRef
5.
go back to reference Mithoefer K, McAdams T, Williams RJ, Kreuz PC, Mandelbaum BR (2009) Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis. Am J Sports Med 37:2053–2063. doi:10.1177/0363546508328414 CrossRefPubMed Mithoefer K, McAdams T, Williams RJ, Kreuz PC, Mandelbaum BR (2009) Clinical efficacy of the microfracture technique for articular cartilage repair in the knee: an evidence-based systematic analysis. Am J Sports Med 37:2053–2063. doi:10.​1177/​0363546508328414​ CrossRefPubMed
6.
go back to reference Gomoll AH, Probst C, Farr J, Cole BJ, Minas T (2009) The use of type I/III bi-layer collagen membrane to decrease re-operation rates for symptomatic hypertrophy after autologous chondrocyte implantation. Am J Sports Med 37(Suppl):20–23. doi:10.1177/0363546509348477 CrossRef Gomoll AH, Probst C, Farr J, Cole BJ, Minas T (2009) The use of type I/III bi-layer collagen membrane to decrease re-operation rates for symptomatic hypertrophy after autologous chondrocyte implantation. Am J Sports Med 37(Suppl):20–23. doi:10.​1177/​0363546509348477​ CrossRef
7.
go back to reference Cavallo C, Desando G, Facchini A, Grigolo B (2010) Chondrocytes from patients with osteoarthritis express typical extracellular matrix molecules once grown onto a three-dimensional hyaluronan-based scaffold. J Biomed Mater Res A 93:86–95. doi:10.1002/jbm.a.32547 PubMed Cavallo C, Desando G, Facchini A, Grigolo B (2010) Chondrocytes from patients with osteoarthritis express typical extracellular matrix molecules once grown onto a three-dimensional hyaluronan-based scaffold. J Biomed Mater Res A 93:86–95. doi:10.​1002/​jbm.​a.​32547 PubMed
13.
go back to reference Tuan RC (2014) Cellular signaling in developmental chondrogenesis: N-cadherin Wnts and BMP-2. J Bone Joint Surg 85-A(2):137–141 Tuan RC (2014) Cellular signaling in developmental chondrogenesis: N-cadherin Wnts and BMP-2. J Bone Joint Surg 85-A(2):137–141
16.
go back to reference Quintana L, Nieden NI, Semino CE (2009) Morphogenetic and regulatory mechanisms during developmental chondrogenesis: New paradigms for cartilage tissue engineering. Tissue Eng Part B Rev 1:29–41. doi: 10.1089/ten.teb.2008.0329 Quintana L, Nieden NI, Semino CE (2009) Morphogenetic and regulatory mechanisms during developmental chondrogenesis: New paradigms for cartilage tissue engineering. Tissue Eng Part B Rev 1:29–41. doi: 10.1089/ten.teb.2008.0329
27.
go back to reference Eslaminejad MB, Fani N, Shahhoseini M (2013) Epigenetic regulation of osteogenic and chondrogenic differentiation of mesenchymal stem cells in culture. Cell J 15:1–10PubMedCentralPubMed Eslaminejad MB, Fani N, Shahhoseini M (2013) Epigenetic regulation of osteogenic and chondrogenic differentiation of mesenchymal stem cells in culture. Cell J 15:1–10PubMedCentralPubMed
30.
go back to reference Rui YF, Lui PPY, Lee YW, Chan KM (2012) Higher BMP receptor expression and BMP-2 induced osteogenic differentiation in tendon-derived stem cells compared with bone-marrow-derived mesenchymal stem cells. Int Orthop 35(5):1099–1107. doi:10.1007/s00264-011-1417-1 CrossRef Rui YF, Lui PPY, Lee YW, Chan KM (2012) Higher BMP receptor expression and BMP-2 induced osteogenic differentiation in tendon-derived stem cells compared with bone-marrow-derived mesenchymal stem cells. Int Orthop 35(5):1099–1107. doi:10.​1007/​s00264-011-1417-1 CrossRef
31.
go back to reference Furumatsu T, Ozaki T (2010) Epigenetic regulation in chondrogenesis. Acta Med Okayama 64(3):155–161PubMed Furumatsu T, Ozaki T (2010) Epigenetic regulation in chondrogenesis. Acta Med Okayama 64(3):155–161PubMed
33.
go back to reference Das SP, Ganesh S, Pradhan S, Singh D, Mohanty RN (2014) Effectiveness of recombinant human bone morphogenetic protein-7 in the management of congenital pseudoarthrotis of the tibia: a randomized controlled trial. Int Orthop 38(9):1987–1992. doi:10.1007/s00264-014-2361-7 CrossRefPubMed Das SP, Ganesh S, Pradhan S, Singh D, Mohanty RN (2014) Effectiveness of recombinant human bone morphogenetic protein-7 in the management of congenital pseudoarthrotis of the tibia: a randomized controlled trial. Int Orthop 38(9):1987–1992. doi:10.​1007/​s00264-014-2361-7 CrossRefPubMed
36.
go back to reference Mihelic R, Pecina M, Jelic M et al (2004) Bone morphogenetic protein-7 (Ostegenetic Proteic-1) promotes tendon graft integration in anterior cruciate ligament reconstruction in sheep. Am J Sports Med 32(7):1619–1625. doi:10.1177/0363546504263703 CrossRefPubMed Mihelic R, Pecina M, Jelic M et al (2004) Bone morphogenetic protein-7 (Ostegenetic Proteic-1) promotes tendon graft integration in anterior cruciate ligament reconstruction in sheep. Am J Sports Med 32(7):1619–1625. doi:10.​1177/​0363546504263703​ CrossRefPubMed
37.
go back to reference Zoricic S, Maric I, Bobinac D, Vukicevic S (2003) Expression of bone morphogenetic proteins and cartilage-derived morphogenetic proteins during osteophyte formation in humans. J Anat 202(Pt 3):269–277CrossRefPubMedCentralPubMed Zoricic S, Maric I, Bobinac D, Vukicevic S (2003) Expression of bone morphogenetic proteins and cartilage-derived morphogenetic proteins during osteophyte formation in humans. J Anat 202(Pt 3):269–277CrossRefPubMedCentralPubMed
41.
go back to reference Longobardi L, Rear LO, Aakula S et al (2006) Effect of IGF-I in the chondrogenesis of bone marrow mesenchymal stem cells in the presence or absence of TGF- β signaling. J Bone Miner Res 21(4):626–636. doi:10.1359/JBMR.051213 CrossRefPubMed Longobardi L, Rear LO, Aakula S et al (2006) Effect of IGF-I in the chondrogenesis of bone marrow mesenchymal stem cells in the presence or absence of TGF- β signaling. J Bone Miner Res 21(4):626–636. doi:10.​1359/​JBMR.​051213 CrossRefPubMed
46.
go back to reference Murtaugh LC, Chyung JH, Lassar a B (1999) Sonic hedgehog promotes somitic chondrogenesis by altering the cellular response to BMP signaling. Genes Dev 13:225–237CrossRefPubMedCentralPubMed Murtaugh LC, Chyung JH, Lassar a B (1999) Sonic hedgehog promotes somitic chondrogenesis by altering the cellular response to BMP signaling. Genes Dev 13:225–237CrossRefPubMedCentralPubMed
49.
go back to reference Kim YI, Ryu J-S, Yeo JE, Choi YJ, Kim YS, Ko K, Koh Y-G (2014) Overexpression of TGF-β1 enhances chondrogenic differentiation and proliferation of human synovium-derived stem cells. Biochem Bioph Res Co 450(4):1593–1599. doi:10.1016/j.bbrc.2014.07.045 CrossRef Kim YI, Ryu J-S, Yeo JE, Choi YJ, Kim YS, Ko K, Koh Y-G (2014) Overexpression of TGF-β1 enhances chondrogenic differentiation and proliferation of human synovium-derived stem cells. Biochem Bioph Res Co 450(4):1593–1599. doi:10.​1016/​j.​bbrc.​2014.​07.​045 CrossRef
50.
go back to reference Shintani N, Siebenrock KA, Hunziker EB (2014) TGF-β1 enhances the BMP-2-induced chondrogenesis of bovine synovial explants and arrests downstream differentiation at an early stage of hypertrophy. PLoS ONE 8(1):e53086. doi:10.1371/journal.pone.0053086 CrossRef Shintani N, Siebenrock KA, Hunziker EB (2014) TGF-β1 enhances the BMP-2-induced chondrogenesis of bovine synovial explants and arrests downstream differentiation at an early stage of hypertrophy. PLoS ONE 8(1):e53086. doi:10.​1371/​journal.​pone.​0053086 CrossRef
52.
go back to reference Ball LM (2007) Intensive care and outcome in children undergoing haematopoietic stem cel transplantaion. Rep Pract Oncol Radiother 12(3):171–174CrossRef Ball LM (2007) Intensive care and outcome in children undergoing haematopoietic stem cel transplantaion. Rep Pract Oncol Radiother 12(3):171–174CrossRef
53.
go back to reference Slovacek L, Slovackova B, Macingova Z, Jebavy L (2007) Sexuality of men treated with hematopoietic stem cell transplantation: a review of the literature. Rep Pract Oncol Radiother 12(5):2770282CrossRef Slovacek L, Slovackova B, Macingova Z, Jebavy L (2007) Sexuality of men treated with hematopoietic stem cell transplantation: a review of the literature. Rep Pract Oncol Radiother 12(5):2770282CrossRef
55.
go back to reference Slovacek L, Slovackova B (2007) Quality of life in oncological and hematooncological patients after hematopietic stem cell transplantation: the effect of selected psychosocial and helath aspects on quality of life: A review of the literature. Rep Pract Radiother 12(1):53–59CrossRef Slovacek L, Slovackova B (2007) Quality of life in oncological and hematooncological patients after hematopietic stem cell transplantation: the effect of selected psychosocial and helath aspects on quality of life: A review of the literature. Rep Pract Radiother 12(1):53–59CrossRef
60.
go back to reference Giuliani N, Lisignoli G, Magnani M et al (2013) New insights into osteogenic and chondrogenic differentiation of human bone marrow mesenchymal stem cells and their potential clinical applications for bone regeneration in pediatric orthopaedics. Stem Cells Int 2013:312501. doi:10.1155/2013/312501 CrossRefPubMedCentralPubMed Giuliani N, Lisignoli G, Magnani M et al (2013) New insights into osteogenic and chondrogenic differentiation of human bone marrow mesenchymal stem cells and their potential clinical applications for bone regeneration in pediatric orthopaedics. Stem Cells Int 2013:312501. doi:10.​1155/​2013/​312501 CrossRefPubMedCentralPubMed
63.
go back to reference Medvedev SP, Shevchenko AI, Zakian SM (2010) Induced pluripotent stem cells : problems and advantages when applying them in regenerative medicine. Acta Nat 2(2):18–28 Medvedev SP, Shevchenko AI, Zakian SM (2010) Induced pluripotent stem cells : problems and advantages when applying them in regenerative medicine. Acta Nat 2(2):18–28
65.
go back to reference Nakayama N, Umeda K (2011) From pluripotent stem cells to essential signalling and cellular intermediates. In: Atwood C (ed) Embryonic stem cells: the hormonal regulation of pluripotency and emryogenesis, InTech. doi:10.5772/589 Nakayama N, Umeda K (2011) From pluripotent stem cells to essential signalling and cellular intermediates. In: Atwood C (ed) Embryonic stem cells: the hormonal regulation of pluripotency and emryogenesis, InTech. doi:10.​5772/​589
66.
69.
go back to reference Illich DJ, Demir N, Stojković M et al (2011) Concise review: induced pluripotent stem cells and lineage reprogramming: prospects for bone regeneration. Stem Cells 29:555–563. doi:10.1002/stem.611 CrossRefPubMed Illich DJ, Demir N, Stojković M et al (2011) Concise review: induced pluripotent stem cells and lineage reprogramming: prospects for bone regeneration. Stem Cells 29:555–563. doi:10.​1002/​stem.​611 CrossRefPubMed
Metadata
Title
The role of growth factors in stem cell-directed chondrogenesis: a real hope for damaged cartilage regeneration
Authors
Ewelina Augustyniak
Tomasz Trzeciak
Magdalena Richter
Jacek Kaczmarczyk
Wiktoria Suchorska
Publication date
01-05-2015
Publisher
Springer Berlin Heidelberg
Published in
International Orthopaedics / Issue 5/2015
Print ISSN: 0341-2695
Electronic ISSN: 1432-5195
DOI
https://doi.org/10.1007/s00264-014-2619-0

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