The Contribution of Adipose Tissue-Derived Mesenchymal Stem Cells and Platelet-Rich Plasma to the Treatment of Chronic Equine Laminitis: A Proof of Concept

Abstract

Laminitis, a highly debilitating disease of the foot in ungulates, is characterized by pathological changes of the complex lamellar structures that maintain the appendicular skeleton within the hoof. Laminitis is a multifactorial disease that involves perturbation of the vascular, hematological, and inflammatory homeostasis of the foot. Interestingly, the pathogenesis of the disease resembles what is observed in metabolic syndromes and sepsis-induced organ failure in humans and animals. We hypothesized that local administration of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) might contribute to establishing an anti-inflammatory and pro-angiogenic environment, and could stimulate the injured tissue in order to restore its functional integrity. According to this assumption, an experimental protocol based on the local intravenous administration of adipose tissue-derived MSCs (aMSCs) in combination with PRP was developed for the treatment of horses affected by chronic laminitis. Nine horses with severely compromised venograms (showing grade III and IV laminitis) that had been unsuccessfully treated with conventional therapies were enrolled. aMSCs and PRP (15 × 106 cells resuspended in 15 mL of PRP) were injected into the lateral or medial digital vein three times, at one-month intervals. The first administration was performed with allogeneic aMSCs, while for the following administrations, autologous aMSCs were used. There was no adverse short-term reaction to the intravenous injection of aMSCs. In the long term, venograms outlined, in all subjects, a progressive amelioration of the vascularization of the foot. An improvement in the structure and function of the hoof was also observed. No adverse events were reported during the follow-up, and the horses returned to a comfortable quality of life. Although the number of animals enrolled in the study is limited, both clinical observations and venography demonstrated an enhancement in the condition of all horses, suggesting that the regenerative therapies in chronic laminitis could be useful, and are worthy of further investigation.

Endothelial cells and angiogenesis in the horse in health and disease—A review

“…The results of Angelone et al. (2017) should be treated with caution, since the study was restricted to only nine horses, which were previously unsuccessfully treated with conventional therapies. Also, there was no control group.…”

“…Sepsis‐related laminitis seems to be the result of two local events. The first is a systemic inflammatory syndrome inducing severe endothelial alteration (Angelone et al., 2017) and the second is the change in digital blood vessel tone and haemodynamics resulting in decreased lamellar blood flow as result of the increase of the post‐capillary resistance. (Allen, Clark, Moore, & Prasse, 1990).…”

“…Angelone et al. (2017) described application of adipose tissue‐derived MSCs in the therapy of equine laminitis. An experimental protocol based on the local intravenous administration of adipose tissue‐derived MSCs in combination with platelet‐rich plasma was developed for the treatment of horses affected by chronic laminitis.…”

“…Angelone et al. (2017) proposed that both adipose tissue‐derived MSCs and PRP could have the potential to contribute to restore a functional vascular network by controlling inflammation, recruiting local cells to restore tissue, lowering ROS and MMP damage, stabilizing vascular walls and promoting neoangiogenesis. The results of Angelone et al.…”

Equine adipose tissue derived stem cells and their multilineage differentiation

“…In animals, application of stem cells is getting more important and gaining momentum day by day. In horse, stem cell therapy for cases like tendinitis (Rivera et al 2020), laminitis (Angelone et al 2017) has brought about a new dimension in veterinary medicine. Autologous and allogenic applications of equine adipose tissue derived stem cells (EASCs) have become a focus for therapeutic purposes.…”