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Evergem, Belgium

Spaas J.H.,ANACURA Group | Broeckx S.Y.,ANACURA Group | Chiers K.,Ghent University | Ferguson S.J.,ETH Zurich | And 8 more authors.
Cellular Physiology and Biochemistry | Year: 2015

Background: Clinical results of regenerative treatments for osteoarthritis are becoming increasingly significant. However, several questions remain unanswered concerning mesenchymal stem cell (MSC) adhesion and incorporation into cartilage. Methods: To this end, peripheral blood (PB) MSCs were chondrogenically induced and/or stimulated with pulsed electromagnetic fields (PEMFs) for a brief period of time just sufficient to prime differentiation. In an organ culture study, PKH26 labelled MSCs were added at two different cell densities (0.5 x106 vs 1.0 x106). In total, 180 explants of six horses (30 per horse) were divided into five groups: no lesion (i), lesion alone (ii), lesion with naïve MSCs (iii), lesion with chondrogenically-induced MSCs (iv) and lesion with chondrogenically-induced and PEMF-stimulated MSCs (v). Half of the explants were mechanically loaded and compared with the unloaded equivalents. Within each circumstance, six explants were histologically evaluated at different time points (day 1, 5 and 14). Results: COMP expression was selectively increased by chondrogenic induction (p = 0.0488). PEMF stimulation (1mT for 10 minutes) further augmented COL II expression over induced values (p = 0.0405). On the other hand, MSC markers remained constant over time after induction, indicating a largely predifferentiated state. In the unloaded group, MSCs adhered to the surface in 92.6% of the explants and penetrated into 40.7% of the lesions. On the other hand, physiological loading significantly reduced surface adherence (1.9%) and lesion filling (3.7%) in all the different conditions (p < 0.0001). Remarkably, homogenous cell distribution was characteristic for chondrogenic induced MSCs (+/- PEMFs), whereas clump formation occurred in 39% of uninduced MSC treated cartilage explants. Finally, unloaded explants seeded with a moderately low density of MSCs exhibited greater lesion filling (p = 0.0022) and surface adherence (p = 0.0161) than explants seeded with higher densities of MSCs. In all cases, the overall amount of lesion filling decreased from day 5 to 14 (p = 0.0156). Conclusion: The present study demonstrates that primed chondrogenic induction of MSCs at a lower cell density without loading results in significantly enhanced and homogenous MSC adhesion and incorporation into equine cartilage. © 2015 S. Karger AG, Basel.

Spaas J.H.,ANACURA Group | Gomiero C.,University of Padua | Broeckx S.Y.,ANACURA Group | Van Hecke L.,Ghent University | And 4 more authors.
Cytotherapy | Year: 2016

Background aims: Several cytokines and growth factors play an essential role in skin regeneration and epithelial-like stem cells (EpSCs) have beneficial effects on wound healing in horses. However, there are no reports available on the expression of these growth factors and cytokines after EpSC therapy. Methods: Wounds of 6 cm2 were induced in the gluteus region of 6 horses and treated with (i) autologous EpSCs, (ii) allogeneic EpSCs, (iii) vehicle treatment or (iv) untreated control. Real time polymerase chain reaction was performed on tissue biopsies taken 1 and 5 weeks after these treatments to evaluate mRNA expression of interferon (IFN)-γ, interleukin (IL)-6, vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), insulin-like growth factor (IGF)-1 and epidermal keratin (eKER). Results: One week after treatments, mRNA levels of IL-6 (P = 0.012) and VEGF (P = 0.008) were higher in allogeneic EpSC-treated wounds compared with controls. Also, mRNA levels of IGF-1 were higher at 1 week in both autologous (P = 0.027) and allogeneic (P = 0.035) EpSC-treated wounds. At week 5, all EpSC- and vehicle-treated wounds demonstrated significantly higher IFN-γ, VEGF and eKER mRNA expression compared with controls and compared with their respective levels at week 1. Conclusions: Equine wounds treated with allogeneic EpSCs demonstrate a significant increase in mRNA expression of IL-6, VEGF and IGF-1 in the acute phase. In the longer term, an increase in IFN-γ, VEGF and eKER mRNA was detected in the wounds treated with allogenic EpSCs, autologous EpSCs or their vehicle. © 2016 International Society for Cellular Therapy.

Broeckx S.Y.,ANACURA Group | Borena B.M.,Ghent University | Borena B.M.,Ambo University | Van Hecke L.,Ghent University | And 7 more authors.
Cytotherapy | Year: 2015

Background aims: Several studies report beneficial effects of autologous and allogeneic stem cells on wound healing. However, no comparison between autologous versus allogeneic epithelial-like stem cells (EpSCs) has been made so far. For this reason, we first hypothesize that both EpSC types enhance wound healing in comparison to vehicle treatment and untreated controls. Second, on the basis of other studies, we hypothesized that there would be no difference between autologous and allogeneic EpSCs. Methods: Twelve full-thickness skin wounds were created in six horses. Each horse was subjected to (i) autologous EpSCs, (ii) allogeneic EpSCs, (iii) vehicle treatment or (iv) untreated control. Wound evaluation was performed at day 3, 7 and 14 through wound exudates and at week 1, 2 and 5 through biopsies. Results: Wound circumference and surface were significantly smaller in autologous EpSC-treated wounds. A significantly lower amount of total granulation tissue (overall) and higher vascularization (week 1) was observed after both EpSC treatments. Significantly more major histocompatibility complex II-positive and CD20-positive cells were noticed in EpSC-treated wounds at week 2. In autologous and allogeneic groups, the number of EpSCs in center biopsies was low after 1 week (11.7% and 6.1%), decreased to 7.6% and 1.7%, respectively (week 2), and became undetectable at week 5. Conclusions: These results confirm the first hypothesis and partially support the second hypothesis. Besides macroscopic improvements, both autologous and allogeneic EpSCs had similar effects on granulation tissue formation, vascularization and early cellular immune response. © 2015 International Society for Cellular Therapy.

Borena B.M.,Ghent University | Borena B.M.,Ambo University | Martens A.,Ghent University | Broeckx S.Y.,ANACURA Group | And 5 more authors.
Cellular Physiology and Biochemistry | Year: 2015

Mammal skin has a crucial function in several life-preserving processes such as hydration, protection against chemicals and pathogens, initialization of vitamin D synthesis, excretion and heat regulation. Severe damage of the skin may therefore be life-threatening. Skin wound repair is a multiphased, yet well-orchestrated process including the interaction of various cell types, growth factors and cytokines aiming at closure of the skin and preferably resulting in tissue repair. Regardless various therapeutic modalities targeting at enhancing wound healing, the development of novel approaches for this pathology remains a clinical challenge. The time-consuming conservative wound management is mainly restricted to wound repair rather than restitution of the tissue integrity (the so-called 'restitutio ad integrum'). Therefore, there is a continued search towards more efficacious wound therapies to reduce health care burden, provide patients with long-term relief and ultimately scarless wound healing. Recent in vivo and in vitro studies on the use of skin wound regenerative therapies provide encouraging results, but more protracted studies will have to determine whether the effect of observed effects are clinically significant and whether regeneration rather than repair can be achieved. For all the aforementioned reasons, this article reviews the emerging field of regenerative skin wound healing in mammals with particular emphasis on growth factor- and stem cell-based therapies. © 2015 S. Karger AG, Basel.

Quattrocelli M.,Stem Cell Biology and Embryology Unit | Giacomazzi G.,Stem Cell Biology and Embryology Unit | Broeckx S.Y.,ANACURA Group | Ceelen L.,ANACURA Group | And 4 more authors.
Stem Cell Reports | Year: 2016

Induced pluripotent stem cells (iPSCs) hold great potential not only for human but also for veterinary purposes. The equine industry must often deal with health issues concerning muscle and cartilage, where comprehensive regenerative strategies are still missing. In this regard, a still open question is whether equine iPSCs differentiate toward muscle and cartilage, and whether donor cell type influences their differentiation potential. We addressed these questions through an isogenic system of equine iPSCs obtained from myogenic mesoangioblasts (MAB-iPSCs) and chondrogenic mesenchymal stem cells (MSC-iPSCs). Despite similar levels of pluripotency characteristics, the myogenic differentiation appeared enhanced in MAB-iPSCs. Conversely, the chondrogenic differentiation was augmented in MSC-iPSCs through both teratoma and in vitro differentiation assays. Thus, our data suggest that equine iPSCs can differentiate toward the myogenic and chondrogenic lineages, and can present a skewed differentiation potential in favor of the source cell lineage. © 2016 The Authors.

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