Origin of tendon stem cells in situ
- 40 Downloads
Adult stem cells are surveillance repositories capable of supplying a renewable source of progenitors for tissue repair and regeneration to maintain tissue homeostasis throughout life. Many tissue-resident stem cells have been identified in situ, which lays the foundation for studying them in their native microenvironment, i.e. the niche. Within the musculoskeletal system, muscle stem cells have been unequivocally identified in the mouse, which have led to considerable advances in understanding their role in muscle homeostasis and regeneration. On the other hand, for bone and tendon progenitor cells, mesenchymal stem cells have been used as the main in vitro cell model as they can differentiate into osteogenic, chondrogenic and tenogenic fates. Despite considerable efforts and employment of modern tools, the in vivo origins of bone and tendon stem cells remain debated. Tendon regeneration via stem cells is understudied and deserves attention as tendon damage is noted for a bleak, time-consuming recovery and the repaired tendon seldom regains the structural integrity and strength of the native, uninjured state.
Here we review the past efforts and recent studies toward defining adult tendon stem cells and understanding tendon regeneration instead of tendon development. The focus is on adult tendon resident cells in situ and the uncertainty of their roles in regeneration.
A systematic literature search using the Pubmed search engine was conducted encompassing the seminal papers in the tendon field.
Investigation of tendon stem cells in situ is in its infancy mainly due to lack of necessary tools and standardized injury model. We propose a concerted effort toward establishing a comprehensive cell atlas of the tendon, making genetic tools and choosing a reliable injury model for coordinated studies among different laboratories. Increasing our basic understanding should aid future therapeutic innovations to shorten and enhance the tendon repair/regeneration process.
KeywordsTendon stem cells midsubstance sheath injury
Unable to display preview. Download preview PDF.
- Agarwal S, Loder S J, Cholok D, Peterson J, Li J, Breuler C, Cameron Brownley R, Hsin Sung H, Chung M T, Kamiya N, Li S, Zhao B, Kaartinen V, Davis T A, Qureshi A T, Schipani E, Mishina Y, Levi B (2017). Scleraxis-lineage cells contribute to ectopic bone formation in muscle and tendon. Stem Cells, 35(3): 705–710PubMedCrossRefGoogle Scholar
- Ateschrang A, Ahmad S S, Stöckle U, Schroeter S, Schenk S, Ahrend M D (2017). Recovery of ACL function after dynamic intraligamentary stabilization is resultant to restoration of ACL integrity and scar tissue formation. Knee Surg Sports Tramatol ArthroscGoogle Scholar
- Buschmann J, Bürgisser G M (2017). Biomechanics on tendons and ligaments. Zurich: Elsevier, PrintGoogle Scholar
- Covas D T, Panepucci R A, Fontes A M, Silva W A Jr, Orellana M D, Freitas M C, Neder L, Santos A R, Peres L C, Jamur M C, Zago M A (2008). Multipotent mesenchymal stromal cells obtained from diverse human tissues share functional properties and gene-expression profile with CD146 + perivascular cells and fibroblasts. Exp Hematol, 36(5): 642–654PubMedCrossRefGoogle Scholar
- Dyment N A, Breidenbach A P, Schwartz A G, Russell R P, Aschbacher-Smith L, Liu H, Hagiwara Y, Jiang R, Thomopoulos S, Butler D L, Rowe D W (2015). Gdf5 progenitors give rise to fibrocartilage cells that mineralize via hedgehog signaling to form the zonal enthesis. Dev Biol, 405(1): 96–107PubMedPubMedCentralCrossRefGoogle Scholar
- Gaut L, Duprez D (2016). Tendon development and diseases. Dev Biol, 5(1): 5–23Google Scholar
- Guerquin MJ, Charvet B, Nourissat G, Havis E, Ronsin O, Bonnin MA, Ruggiu M, Olivera-Martinez I, Robert N, Lu Y, Kadler K E, Baumberger T, Doursounian L, Berenbaum F, Duprez D (2013). Transcription factor EGR1 directs tendon differentiation and promotes tendon repair. J Clin Invest, 123(8): 3564–3576PubMedPubMedCentralCrossRefGoogle Scholar
- Hall T E, Bryson-Richardson R J, Berger S, Jacoby A S, Cole N J, Hollway G E, Berger J, Currie P D (2007). The zebrafish candyfloss mutant implicates extracellular matrix adhesion failure in laminin 2-deficient congenital muscular dystrophy. Proc Natl Acad Sci USA, 104(17): 7092–7PubMedCrossRefGoogle Scholar
- Kaux J F, Janssen L, Drion P, Nusgens B, Libertiaux V, Pascon F, Heyeres A, Hoffmann A, Lambert C, Le Goff C, Denoël V, Defraigne J O, Rickert M, Crielaard J M, Colige A (2014). Vascular Endothelial Growth Factor-111 (VEGF-111) and tendon healing: preliminary results in a rat model of tendon injury. Muscles Ligaments Tendons J, 4(1): 24–28PubMedPubMedCentralGoogle Scholar
- Letson A K, Dahners L E (1994). The effect of combinations of growth factors on ligament healing. Clin Orthop Relat Res, (308): 207–212Google Scholar
- Petersen J R, Agarwal S, Brownley R C, Loder S J, Ranganathan K, Cederna P S, Mishina Y, Wang S C, Levi B (2015). Direct mouse trauma/burn model for heterotopic ossification. J Vis Exp (102): 52880Google Scholar
- Runesson E, Ackermann P, Karlsson J, Eriksson B I (2015). Nucleostemin-and Oct 3/4-positive stem/progenitor cells exhibit disparate anatomical and temporal expression during rat Achilles tendon healing. BMC Musculoskelet Disord, 16(212): 1Google Scholar
- Snippert H J, van der Flier L G, Sato T, van Es J H, van den Born M, Kroon-Veenboer C, Barker N, Klein A M, van Rheenen J, Simons B D, Clevers H (2010). Intestinal crypt homeostasis results from neutral competition between symmetrically dividing Lgr5 stem cells. Cell, 143(1): 134–144PubMedCrossRefGoogle Scholar
- Urdzikova L M, Sedlacek R, Suchy T, Amemori T, Ruzicka J, Lesny P, Havlas V, Sykova E, Jendelova P (2014). Human multipotent mesenchymal stem cells improve healing after collagenase tendon injury in the rat. Biomed Eng Online, 13(42): 1–15Google Scholar
- Wolfman N M, Hattersley G, Cox K, Celeste A J, Nelson R, Yamaji N, Dube J L, DiBlasio-Smith E, Nove J, Song J J, Wozney J M, Rosen V (1997). Ectopic induction of tendon and ligament in rats by growth and differentiation factors 5, 6, and 7, members of the TGF-beta gene family. J Clin Invest, 100(2): 321–330PubMedPubMedCentralCrossRefGoogle Scholar
- Zampeli F, Terzidis I, Espregueiera-Mendes J, Georgoulis J D, Bernard M, Pappas E, Georgoulis A D (2017). Restoring tibiofemoral alignment during ACL reconstruction results in better knee biomechanics. Knee Surg Sports Traumatol Arthrosc, 25(6): 1367–1374Google Scholar
- Zhang J and Wang J H C (2010). Characterization of differential properties of rabbit tendon stem cells and tenocytes. BMC Musculoskelet Disord, 11(10): 1Google Scholar
- Zhang Y, Kao W W Y, Hayashi Y, Zhang L, Call M, Dong F, Yuan Y, Zhang J, Wang Y C, Yuka O, Shiraishi A, Liu C Y (2017). Generation and characterization of a novel mouse line, Keratocan-rtTA (KeraRT), for corneal stroma and tendon research. Invest Ophthalmol Vis Sci, 58(11): 4800–4808PubMedPubMedCentralCrossRefGoogle Scholar
- Zheng G X Y, Terry J M, Belgrader P, Ryvkin P, Bent Z W, Wilson R, Ziraldo S B, Wheeler T D, McDermott G P, Zhu J, Gregory M T, Shuga J, Montesclaros L, Underwood J G, Masquelier D A, Nishimura S Y, Schnall-Levin M, Wyatt P W, Hindson C M, Bharadwaj R, Wong A, Ness K D, Beppu L W, Deeg H J, McFarland C, Loeb K R, Valente W J, Ericson N G, Stevens E A, Radich J P, Mikkelsen T S, Hindson B J, Bielas J H (2017). Massively parallel digital transcriptional profiling of single cells. Nat Commun, 8: 1–12CrossRefGoogle Scholar