Toepassingen van mesenchymale stamcellen bij het paard: huidige stand van zaken

Mesenchymal stem cells (MSC) are adult stem cells, which are capable of self-renewal and restricted differentiation into multiple organ-specific cell types. The significant therapeutic potential of MSC arises from their ability to promote tissue regeneration, prevent pathological scar formation, modulate immune responses and regulate inflammation. At present, MSC are mainly used in veterinary medicine to treat musculoskeletal injuries. Nevertheless, they may as well play a role in the treatment of several non-orthopedic diseases, such as immune-mediated, ischemic, inflammatory and neurological diseases. The treatment efficiency of MSC therapy can be influenced by the number of MSC which is used to treat the horse, the way the MSC are administered and the timing of the treatment. Moreover, there are advantages as well as disadvantages correlated to the use of autologons versus allogeneic MSC. The use of MSC in the treatment of equine injury has exciting potential. However; more fundamental research and well-designed clinical trials remain mandatory in order to safeguard the optimal routine clinical use of these valuable equine MSC at the patients' benefit

Characterization and profiling of immunomodulatory genes of equine mesenchymal stromal cells from non-invasive sources

Introduction: Mesenchymal stromal cells (MSCs) have been extensively studied for their promising capabilities in regenerative medicine. Although bone marrow is the best-known source for isolating equine MSCs, non-invasive alternative sources such as umbilical cord blood (UCB), umbilical cord matrix (UCM), and peripheral blood (PB) have also been reported. Methods: Equine MSCs from three non-invasive alternative sources were isolated from six individual mares (PB) and their foals (UCB and UCM) at parturition. To minimize inter-horse variability, the samples from the three sources were matched within the same mare and for UCB and UCM even within the same foal from that specific mare. The following parameters were analyzed: (i) success rate of isolation, (ii) proliferation capacity, (iii) tri-lineage differentiation ability, (iv) immunophenotypical protein, and (v) immunomodulatory mRNA profiles. Linear regression models were fit to determine the association between the source of MSCs (UCB, UCM, PB) and (i) the moment of first observation, (ii) the moment of first passage, (iii) cell proliferation data, (iv) the expression of markers related to cell immunogenicity, and (v) the mRNA profile of immunomodulatory factors, except for hepatocyte growth factor (HGF) as no normal distribution could be obtained for the latter variable. To evaluate the association between the source of MSCs and the mRNA expression of HGF, the non-parametric Kruskal-Wallis test was performed instead. Results: While equine MSCs could be isolated from all the UCB and PB samples, isolation from UCM was successful in only two samples because of contamination issues. Proliferation data showed that equine MSCs from all three sources could be easily expanded, although UCB-derived MSCs appeared significantly faster in culture than PB- or UCM-derived MSCs. Equine MSCs from both UCB and PB could be differentiated toward the osteo-, chondro-, and adipogenic lineage, in contrast to UCM-derived MSCs in which only chondro-and adipogenic differentiation could be confirmed. Regardless of the source, equine MSCs expressed the immunomodulatory genes CD40, CD80, HGF, and transforming growth factor-beta (TGF beta). In contrast, no mRNA expression was found for CD86, indoleamine 2,3-dioxygenase (IDO), and tumor necrosis factor-alpha (TNF alpha). Conclusions: Whereas UCM seems less feasible because of the high contamination risks and low isolation success rates, UCB seems a promising alternative MSC source, especially when considering allogeneic MSC use

The effect of a multidisciplinary weight loss program on renal circadian rhythm in obese adolescents

Adolescent obesity is a serious health problem associated with many comorbidities. Obesity-related alterations in circadian rhythm have been described for nocturnal blood pressure and for metabolic functions. We believe renal circadian rhythm is also disrupted in obesity, though this has not yet been investigated. This study aimed to examine renal circadian rhythm in obese adolescents before and after weight loss. In 34 obese adolescents (median age 15.7 years) participating in a residential weight loss program, renal function profiles and blood samples were collected at baseline, after 7 months, and again after 12 months of therapy. The program consisted of dietary restriction, increased physical activity, and psychological support. The program led to a median weight loss of 24 kg and a reduction in blood pressure. Initially, lower diurnal free water clearance (- 1.08 (- 1.40-- 0.79) mL/min) was noticed compared with nocturnal values (0.75 (- 0.89-- 0.64) mL/min). After weight loss, normalization of this inverse rhythm was observed (day - 1.24 (- 1.44-1.05) mL/min and night - 0.98 (- 1.09-- 0.83) mL/min). A clear circadian rhythm in diuresis rate and in renal clearance of creatinine, solutes, sodium, and potassium was seen at all time points. Furthermore, we observed a significant increase in sodium clearance. Before weight loss, daytime sodium clearance was 0.72 mL/min (0.59-0.77) and nighttime clearance was 0.46 mL/min (0.41-0.51). After weight loss, daytime clearance increased to 0.99 mL/min (0.85-1.17) and nighttime clearance increased to 0.78 mL/min (0.64-0.93). Conclusion: In obese adolescents, lower diurnal free water clearance was observed compared with nocturnal values. Weight loss led to a normalization of this inverse rhythm, suggesting a recovery of the anti-diuretic hormone activity. Both before and after weight loss, clear circadian rhythm of diuresis rate and renal clearance of creatinine, solutes, sodium, and potassium was observed.What is Known:center dot Obesity-related alterations in circadian rhythm have been described for nocturnal blood pressure and for metabolic functions. We believe renal circadian rhythm is disrupted in obesity, though this has not been investigated yet.What is New:center dot In obese adolescents, an inverse circadian rhythm of free water clearance was observed, with higher nighttime free water clearance compared with daytime values. Weight loss led to a normalization of this inverse rhythm, suggesting a recovery of the anti-diuretic hormone activity.center dot Circadian rhythm in diuresis rate and in the renal clearance of creatinine, solutes, sodium, and potassium was preserved in obese adolescents and did not change after weight loss

Desmopressin lyophilisate for the treatment of central diabetes insipidus : first experience in very young infants

INTRODUCTION: In neonates and small infants, early diagnosis of central diabetes insipidus (CDI) and treatment with desmopressin in low doses (avoiding severe hypo- or hypernatremia) are important to prevent associated high morbidity and mortality in this particular age group. CASE PRESENTATION: We described pharmacokinetic and pharmacodynamic results of the use of recently launched oral desmopressin lyophilisate (Minirin Melt®) in two infants with CDI, diagnosed at the age of 12 and 62 days, respectively. We observed that a starting dose of 60 μg of Minirin Melt® in the first case resulted in a pharmacokinetic profile largely exceeding the reference frame observed in children with nocturnal enuresis, while a dose of 15 μg in the second case resulted in acceptable concentrations. After initial dose adjustments, administration of sublingual lyophilisate resulted in rather stable serum sodium concentrations. CONCLUSIONS: Using Minirin Melt® in infants with CDI appears to be effective, easy to use and well tolerated

Treatment of equine degenerative joint disease with autologous peripheral blood-derived mesenchymal stem cells: a case report

A 5-year-old German Warmblood stallion with chronic lameness, attributable to degenerative joint disease (DJD) of the pastern joint unresponsive to medical treatments, was treated with autologous mesenchymal stem cells (MSC). These MSC were isolated from the peripheral blood (PB) of the patient and injected into the pastern joint, at a concentration of 2.5x10(6) cells, twice with an 8-week interval. The positive response to this stem cell treatment was documented by visual gait evaluation as well as objective pressure plate analyses. This paper is the first to describe the use of autologous PB-derived MSC to treat a horse suffering from chronic DJD. The favorable outcome of this single case may stimulate further research on the use of equine peripheral blood as a source of autologous MSC in equine regenerative medicine