Effect of single intralesional treatment of surgically induced equine superficial digital flexor tendon core lesions with adipose-derived mesenchymal stromal cells: a controlled experimental trial

Abstract

BackgroundAdipose tissue is a promising source of mesenchymal stromal cells (MSCs) for the treatment of tendon disease. The goal of this study was to assess the effect of a single intralesional implantation of adipose tissue-derived mesenchymal stromal cells (AT-MSCs) on artificial lesions in equine superficial digital flexor tendons (SDFTs).MethodsDuring this randomized, controlled, blinded experimental study, either autologous cultured AT-MSCs suspended in autologous inactivated serum (AT-MSC-serum) or autologous inactivated serum (serum) were injected intralesionally 2 weeks after surgical creation of centrally located SDFT lesions in both forelimbs of nine horses. Healing was assessed clinically and with ultrasound (standard B-mode and ultrasound tissue characterization) at regular intervals over 24 weeks. After euthanasia of the horses the SDFTs were examined histologically, biochemically and by means of biomechanical testing.ResultsAT-MSC implantation did not substantially influence clinical and ultrasonographic parameters. Histology, biochemical and biomechanical characteristics of the repair tissue did not differ significantly between treatment modalities after 24 weeks. Compared with macroscopically normal tendon tissue, the content of the mature collagen crosslink hydroxylysylpyridinoline did not differ after AT-MSC-serum treatment (p = 0.074) while it was significantly lower (p = 0.027) in lesions treated with serum alone. Stress at failure (p = 0.048) and the modulus of elasticity (p = 0.001) were significantly lower after AT-MSC-serum treatment than in normal tendon tissue.ConclusionsThe effect of a single intralesional injection of cultured AT-MSCs suspended in autologous inactivated serum was not superior to treatment of surgically created SDFT lesions with autologous inactivated serum alone in a surgical model of tendinopathy over an observation period of 22 weeks. AT-MSC treatment might have a positive influence on collagen crosslinking of remodelling scar tissue. Controlled long-term studies including naturally occurring tendinopathies are necessary to verify the effects of AT-MSCs on tendon disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0564-8) contains supplementary material, which is available to authorized users.

Uptake of magnetic nanoparticles for adipose-derived stem cells with multiple passage numbers

“…The sources of MSCs are diverse and those derived from adipose tissue have immune exemption characteristics [9] and the ability to inhibit activated lymphocyte proliferation in allografts [10]. Thus, the adipose-derived mesenchymal stem cells (ADSCs) are especially suitable for clinical availability and application [11]. Despite this, an important clinical issue is that the number of freshly obtained stem cells in vivo is often too small to meet practical demand.…”

Mechanisms of Action of Multipotent Mesenchymal Stromal Cells in Tendon Disease

“…Animal species used comprise small (rats [54, [106][107][108][109][110][111][112][113][114][115][116][117][118] and rabbits [119][120][121][122]) and large animals (dogs [123][124][125][126], sheep [127][128][129], and horses [130][131][132][133][134][135][136][137][138][139][140][141]).…”

“…In conjunction with the synthesis and protection of desired ECM components such as collagen I, this could be due to active ECM remodeling and the contribution of synthesized small ECM molecules to collagen fibrillogenesis. Still, it should be acknowledged that some studies in the equine model could demonstrate only few compositional or structural improvements 5 months after ASC treatment [133,137]. Moreover, despite generally improved ECM structure and collagen I synthesis, collagen II deposits and areas staining positive for alizarin red were found in BMSC-treated tendons [106], suggesting that erroneous MSC differentiation toward the chondrogenic and osteogenic lineage had occurred.…”

Reduction of Recurrent Tendinitis Scar Using Autologous Mesenchymal Stem Cells Derived from Adipose Tissue from the Base of the Tail in Holsteiner Horses (Equus ferus caballus)

“…This produces tendon repair with a stable cell matrix, providing greater support to this structure and enabling the horse to return to race training (Kol et al, 2013). Stem cells derived from adult tissues can participate in tissue regeneration through different mechanisms: by direct contribution, through phenotype differentiation of specific cells in the tissue, by generating ECM, by increasing the size of blood vessels and by remodelling the scar tissue (Nixon et al, 2008;Conze et al, 2014;Geburek et al, 2017). MSC can be obtained from various sources in adults; they can be extracted from bone marrow, perivascular tissue, blood, tendons, muscle and adipose tissue.…”