Tendon Research Group Presents The Role Of Tendon Stem Cells In Tendon Disease And Repair




Organiser: PD Dr. Denitsa Docheva,

Experimed, Dep. of Surgery, Ludwig-Maximilians-University, Munich, Germany


Aim: Our research group is based in the Ludwig-Maximilians-University (LMU) of Munich and is primarily focusing on understanding tendon biology and repair mechanisms. In contrast to the other musculoskeletal tissues, tendons are poorly investigated, which correlates with the lack of efficient tendon-specific therapeutics. To counter this lag in the tendon field, we have established over the years valuable in vitro and in vivo models. These are suitable to address different basic scientific, but also clinical questions and to carry out up-to-date analyses of tendons. In our course, we will provide clear guidelines to the participants on how to study tendon gene function and stem cell behavior in vitro as well as on how to implement knockout mouse lines and to develop pre-clinical animal for testing novel repair options for tendons. We believe that such cumulative efforts can tremendously enrich our knowledge and can result in major breakthroughs in the management of tendon diseases. Our course will be very beneficial for basic scientists and clinicians doing experimental research.




Outcome 1: To update and overview the latest approaches for augmenting tendon repair. (Introduction)

Outcome 2: To learn about the present state of tendon biology and specifically about a) crucial tendon-specific genes, b) definition and features of tendon stem cells, c) difference between tendon stem cells other stem cell types and d) stem cells connection to tendon diseases. (In vitro part)

Outcome 3: To learn powerful in vivo technologies for tendon research and specifically about a) knockout technology, b) knockout mouse models with tendon phenotype, c) animal models for tendon injury and d) stem cells effect on tendon healing. (In vivo part)



Preliminary program:


1. Introduction:



"Current strategies for tendon repair"

(PD. Dr. Denitsa Docheva, 15 min)









2. In vitro models:



"Gene control of the tendon stem cell niche"

(M.Sc. Sarah Dex, 20 min)











"Dysregulation of stem cells in tendon aging and degeneration"

(Dr. Cvetan Popov, 20 min)









3. In vivo models:



"The use of knockout mouse models for understanding tendons"

(Dr. Paolo Alberton, 20 min)











"Stem cells in tendon tissue engineering"

(M.Sc. Chi-fen Hsieh, 20 min)










4. Summary and open discussion (moderator PD Dr. Denitsa Docheva 25 min)



Biographies and publications


Denitsa Docheva (PD; PhD) is the principal investigator and the group leader of the Munich Tendon Research Group. The group was established in 2006 and at present consists of 2 post doctors Cvetan Popov (PhD) and Paolo Alberton (PhD) and two PhD students Sarah Dex and Chi-fen Hsies (both M.Sc.). All members and projects are financed by prestigious research grants (German research Foundation (DFG), AO Research Foundation, DAAD and etc.). Our scientific achievements from the last years have been published in multiple research papers dealing with tendon molecular biology, human and mouse stem cells, knockout models and tissue engineering. Moreover, we have been awarded several scientific prizes from international or German associations and meetings.


1. Publications:


Docheva D, Müller SA, Majewski M, Evans C. Biologics for tendon repair. Adv Drug Deliv Rev. 2014; Nov 21. pii: S0169-409X(14)00278-6. doi: 10.1016/j.addr.2014.11.015. [Epub ahead of print] Review.

Alberton P, Dex S, Popov C, Shukunami C, Schieker M, Docheva D. Loss of tenomodulin results in reduced self-renewal and augmented senescence of tendon stem/ progenitor cells. Stem Cells Dev. 2014; Oct 28. [Epub ahead of print]

Docheva D, Popov C, Alberton P, Aszodi A. Integrin signaling in skeletal development and function. Birth Defects Res C Embryo Today 2014; 102(1):13-36. Review.

Wagenhäuser MU, Pietschmann MF, Docheva D, Gülecyüz MF, Jansson V, Müller PE. Assessment of essential characteristics of two different scaffolds for tendon in situ regeneration. Knee Surg Sports Traumatol Arthrosc. 2014; Jan 4. [Epub ahead of print]

Kohler J, Popov C, Klotz B, Alberton P, Prall WC, Haasters F, Müller-Deubert S, Ebert R, Klein-Hitpass L, Jakob F, Schieker M, Docheva D. Uncovering the cellular and molecular changes in tendon stem/progenitors cells attributed to tendon aging and degeneration. Aging Cell. 2013; 12(6):988-99.

Komiyama Y, Ohba S, Shimohata N, Nakajima K, Hojo H, Yano F, Takato T, Docheva D, Shukunami C, Hiraki Y, Chung UL. Tenomodulin expression in the periodontal ligament enhances cellular adhesion. PLoS ONE 2013; 8(4):e60203.

Pietschmann MF, Frankewycz B, Schmitz P, Docheva D, Sievers B, Jansson V, Schieker M, Müller PE. Comparison of tenocytes and mesenchymal stem cells seeded on biodegradable scaffolds in a full-size tendon defect model. J Mater Sci Mater Med. 2013; 24(1):211-20.

Alberton P, Prägert M, Popov C, Kohler J, Shukunami C, Schieker M, Docheva D. Conversion of human bone marrow-derived mesenchymal stem cells into tendon progenitor cells by ectopic expression of Scleraxis. Stem Cells Dev. 2012; 21(6):846-58.

Jakob F, Ebert R, Rudert M, Nöth U, Walles H, Docheva D, Schieker M, Meinel L, Groll J. In situ guided tissue regeneration in musculoskeletal diseases and aging: Implementing pathology into tailored tissue engineering strategies. Cell Tissue Res. 2012; 347(3):725-35.

Wagenhäuser MU, Pietschmann MF, Sievers B, Docheva D, Schieker M, Jansson V, Müller PE. Collagen type I and decorin expression in tenocytes depend on the cell isolation method. BMC Musculoskelet Disord. 2012; 13(1):140.

Knothe Tate ML, Tami AE, Netrebko P, Milz S, Docheva D. Multiscale computational and experimental approaches to elucidate bone and ligament mechanobiology using the ulna-radiusinterosseous membrane construct as a model system. Technol Health Care. 2012;20(5):363-78.

Popov C, Radic T, Prall WC, Haasters F, Aszodi A, Gullberg D, Schieker M, Docheva D. Integrins α2β1 and α11β1 regulate the survival of mesenchymal stem cells on collagen I. Cell Death Dis. 2011; 2:e186; doi: 10.1038/cddis.2011.71.

Haasters F, Polzer H, Prall WC, Saller MM, Kohler J, Grote S, Mutschler W, Docheva D, Schieker M. Bupivacaine, Ropivacaine and Morphine: Comparison of Toxicity on Human Hamstring-derived Stem/Progenitor Cells. Knee Surg Sport Tr A. 2011; 19(12):2138-44.

Docheva D, Padula D, Popov C, Weishaupt P, Prägert M, Miosge N, Hickel R, Böcker W, Clausen-Schaumann H, Schieker M. Establishment of immortalized periodontal ligament progenitor cell line and its behavioural analysis on smooth and rough titanium surface. Eur Cells Mater. 2010; 19:228-241.

Kimura N, Shukunami C, Hakuno D, Yoshioka M, Miura S, Docheva D, Kimura T, Okada Y, Matsumura G, Shin'oka T, Yozu R, Kobayashi J, Ishibashi-Ueda H, Hiraki Y, Fukuda K. Local tenomodulin absence, angiogenesis, and matrix metalloproteinase activation are associated with the rupture of the chordae tendineae cordis. Circulation. 2008; 118(17):1737-1747.

Docheva D, Popov C, Mutschler W, Schieker M. Human mesenchymal stem cells in contact with their environment: surface characteristics and the integrin system. J Cell Mol Med. 2007; 11(1):21-38. Review.

Docheva D, Hunziker EB, Fässler R, Brandau O. Tenomodulin is necessary for tenocyte proliferation and tendon maturation. Mol Cell Biol. 2005; 25(2):699-705.


2. Awards:


2014, CF. Hsieh et al., Poster Award at the Osteology Congress, Munich; Germany

2013, CF. Hsieh, Travel Award of the GSK Foundation

2011, D. Docheva, EORS Exchange Travel Award

D. Docheva, VSOU Young Investigator Award (2nd Place)

D. Docheva, Friedrich Heuck Osteology Prise (2nd Place)

2010, M. Pietschmann et al., Poster Award at the 18th EORS Congress, Davos, Switzerland

2009, D. Docheva, Travel Award of the European Science Foundation

2008, D. Docheva, Award for Top 10 Cited Paper 2007-2008. J. of Cellular and Molecular Medicine


Tendon Research Group Presents The Role Of Tendon Stem Cells In Tendon Disease And Repair