Table 1.
Biochemical strategies of tenogenic differentiation
| Supplementation | Target cell | Optimal concentration | Treatment time | Outcome | References |
|---|---|---|---|---|---|
| CTGF with ascorbic acid | Human BMSC | 100 ng/ml | 4 weeks | COL I and TN‐C contents↑ | Lee CH, et al. Conf Proc IEEE Eng Med Biol Soc 2006 |
| Human BMSC | 100 ng/ml | 4 weeks | COL I, COL III, TN‐C, FN, VIM, MMP‐1 (4–10 folds↑); COL I and TN‐C contents↑ | Lee CH, et al. J Clin Invest 2010 | |
| Rat TSPC | 25 ng/ml | 2 weeks | Tnmd, Scx, Thbs4 (1–2 folds↑); Col1a1, Eln, Dcn, Bgn (1–3 folds↑) | Ni M, et al. Biomaterials 2013 | |
| Rat TSPC | 25 ng/ml | 2 weeks | Col1a1, Tnmd ↑; chondrogenic (Acan, Col2a1) and osteogenic (Alpl) markers↓ | Lui PP, et al. Cytotherpy 2016 | |
| Rat CD146+ tendon cell | 100 ng/ml | 1 week | Col1a1, Col3a1, Tn‐C, Vim, Tnmd and Scx (3–25 folds↑) | Lee CH, et al. J Clin Invest 2015 | |
| TGF‐β1 | Mouse flexor tendon tenocyte | 10 or 100 ng/ml | 24, 48 hours | Mmp‐16, Dcn↓; Bgn, Col V, Col XII, Serpine1, Scx, and Mkx (5–10 folds↑) | Farhat YM, et al. PLoS One 2012 |
| TGF‐β2 | Mouse MSC | 20 ng/ml | 1, 24 hours | Scx (6–8 folds↑) and Col1a1 (3–4 folds↑) | Guerquin MJ, et al. J Clin Invest 2013 |
| Mouse TSPC and MSC | / | 12, 24, 48 hours | Scx (6–8 folds↑), Col1a1 (3–4 folds↑), Col5a1 (2–3 folds↑) at different time points | Liu H, et al. Stem Cells 2015 | |
| TGF‐β2/3 | Mouse MSC (C3H10T1/2) | 20 ng/ml | 24 hours | Scx (6–8 folds↑), Col1a1(3–4 folds↑), Sox9 (4–6 folds↓) | Havis E, et al. Development 2014 |
| TGF‐β3 | Human bone marrow‐derived mononuclear cells | 20 ng/ml | 7 days | Synthesis of collagen fibrils and appearance of fibripositors | Kapacee Z, et al. Matrix Biol 2010 |
| Equine embryo‐derived stem cells | 20ng/ml | 72 hours | Scx, Tn‐C, Col1a1, and cartilage oligomeric matrix protein (Comp) ↑ | Barsby T, et al. Tissue Eng Part A 2013 | |
| GDF‐5 (BMP‐14) | Rat ADSC | 100 ng/ml | 3, 6, 9, and 12 days |
ECM (Col I, Dcn, Acan) and tenogenic marker gene (Scx, Tnmd, and Tn‐C) expression↑ Tnmd, Tn‐C, Smad‐8, and Mmp‐13 protein expression↑ |
Park A, et al. Tissue Eng Part A 2010 |
| Human BMSC | 100 ng/ml | 4 days | COL I, SCX, and TN‐C expression (2.31 ± 0.27, 2.30 ± 1.81 and 3.55 ± 0.27 folds↑) | Tan SL, et al. Cells Tissues Organs 2012 | |
| P4–6 periodontal ligament‐derived cells | 10 ng/ml | 3 weeks | SCX (2 folds↑), TNMD markedly, ACAN and COL III (4–8 folds↑) | Xia D, et al. Growth Factors 2013 | |
| Human BMSC | / | 3 days | COL1A1, COL3A1, DCN, SCX, and TN‐C↑ | Govoni M, et al. Tissue Eng Part A 2017 | |
| GDF‐6 (BMP‐13) | Mouse BMSC | 100 nM | 3 days | Col I (3 folds↑), Thbs4 (10 folds↑) | Berasi SP, et al. Growth Factors 2011 |
| Rat BMSC | 20 ng/ml | 2 weeks |
Tnmd (5.61 folds↑) and Scx (4.18 folds↑), Tnmd protein expression↑ |
Chai W, et al. Chin Med J (Engl) 2013 | |
| GDF‐7 (BMP‐12) | Horse BMSC | 50 ng/ml | 14–21 days | Tnmd and Dcn expression | Violini S, et al. BMC Cell Biol 2009 |
| Mouse BMSC | 100 nM | 3 days | Col I (3 folds↑), Thbs4 (12 folds↑) | Berasi SP, et al. Growth Factors 2011 | |
| Rat BMSC | 10 ng/ml | 12 hours | Scx, Tnmd, Tn‐C, Col I (2–4 folds↑) | Lee JY, et al. PLoS One 2011 | |
| Rat BMSC | 50 ng/ml | 2 weeks | Scx (2.56 folds↑), Tnmd (3.07 folds↑), Tn‐C (1.88 folds↑), Tnmd protein expression↑ | Ni M, et al. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2011 | |
| Canine/Mouse ADSC | 100 or 1,000 ng/ml | 3, 7, 14 days | Scx, Tnmd gene, and protein expression↑ | Shen H, et al. PLoS One 2013 | |
| Rat TSPC | 50 ng/ml | 14 days | Scx, Tnmd, Col I, and Tn‐C gene, and protein expression↑ | Liu J, et al. Cell Physiol Biochem 2015 | |
| FGF‐2 | Human BMSC | 3 ng/ml | 14 days | COL I, COL III, FN expression (1–2 folds↑) | Hankemeier S, et al. Tissue Eng 2005 |
| FGF‐2 or PDGF‐BB | Canine flexor tendon fibroblast | 10 ng/ml | 24 hours | Cell proliferation and collagen production↑ | Thomopoulos S, et al. J Hand Surg Am 2005 |
| PD18 (a mitogen‐activated protein kinase inhibitor) | Mouse MSC | 3.3 µM | 24 hours | Scx and Col1a1 (∼2 folds↑) | Havis E, et al. Development 2014 |
| Wnt 3a | Mouse MSC | / | 48 hours | Scx promoter, luciferase assay | Zhu X, et al. Development Biology 2012 |
| BIO (a glycogen synthase kinase‐3 inhibitor) | Equine BMSC | 10 μM | 7 days | Tnmd (∼3 folds↑), Col14a1, Dcn, and Fmod gene expression↑ | Miyabara S, et al. J Equine Sci 2014 |
| BMP2 + Smad8 | Mouse MSC | / | 4, 7, 10, 14 days | Morphological characteristics and gene expression profile of tendon cells both in vitro and in vivo | Hoffmann A, et al. J Clin Invest 2006 |
| Recombinant human adiponectin | Diabetic ridden human TSPC | 10 μg/ml | 48 hours | COL I, III, TNMD, and SCX expression (2.0 ± 0.3, 1.73 ± 0.25, 1.63 ± 0.21 and 1.74 ± 0.24 folds↑) | Rothan HA, et al. Int J Med Sci 2013 |
Abbreviations: /, not determined; ADSC, adipose‐derived mesenchymal stem cells; BMSC, bone marrow stromal cells; COL I, type I collagen; CTGF, connective tissue growth factor; FGF, fibroblast growth factor; GDF, growth differentiation factor; MSC, mesenchymal stem cells; PDGF‐BB, platelet‐derived growth factors; TGF‐β, transforming growth factor beta; TN‐C, tenascin‐C; TSPC, tendon stem/progenitor cells.