4.7 Article

Crosstalk between adipose stem cells and tendon cells reveals a temporal regulation of tenogenesis by matrix deposition and remodeling

Journal

JOURNAL OF CELLULAR PHYSIOLOGY
Volume 233, Issue 7, Pages 5383-5395

Publisher

WILEY
DOI: 10.1002/jcp.26363

Keywords

adipose-derived stem cells; co-culture; extracellular matrix; matrix metalloproteinases; temporal gene regulation; tendon regeneration

Funding

  1. Fundacao para a Ciencia e a Tecnologia [IF/00593/2015, PD/BD/128088/2016, SFRH/BD/96593/2013]
  2. European Regional Development Fund [RL3-TECT-NORTE-07-0124-FEDER-000020]

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Tendon injuries constitute an unmet clinical challenge owing to the limited intrinsic regenerative ability of this tissue. Cell-based therapies aim at improving tendon healing through the delicate orchestration of tissue rebuilding and regain of function. Hence, human adipose-derived stem cells (hASCs) have been proposed as a promising cell source for boosting tendon regeneration. In this work, we investigated the influence of hASCs on native human tendon-derived cells (hTDCs) through the establishment of a direct contact co-culture system. Results demonstrated that direct interactions between these cell types resulted in controlled proliferation and spontaneous cell elongation. ECM-related genes, particularly COL1A1 and TNC, and genes involved in ECM remodeling, such as MMP1, MMP2, MMP3, and TIMP1, were expressed in co-culture in a temporally regulated manner. In addition, deposition of collagen type I was accelerated in co-culture systems and favored over the production of collagen type III, resulting in an enhanced COL1/COL3 ratio as soon as 7 days. In conclusion, hASCs seem to be good candidates in modulating the behavior of native tendon cells, particularly through a balanced process of ECM synthesis and degradation.

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