Transplantation (Tx) of skeletal myoblasts (SM) within an infarcted myocardium improves global left ventricular (LV) function, although a direct systolic effect remains controversial.
Global and ...regional LV functions were studied in a sheep model (n=16) of infarction before (baseline), and 4 (M4), and 12 (M12) months after in-scar injections of autologous SM or culture medium (CM). LV end-diastolic volume (EDV), ejection fraction (EF), wall motion score (WMS), and systolic myocardial velocity gradient (MVG) across the scar were measured by echocardiography with tissue Doppler imaging. Parameters were similar at baseline between groups. At M4, Tx of SM reduced the postinfarction increase in EDV (72+/-8 versus 105+/-13 mL in the CM group, P<0.05) and the decrease in EF (48+/-5 versus 33+/-3% in the CM group, P=0.006) although it improved WMS (5.4+/-1.2 versus 13+/-2.2 in the CM group, P<0.01) and SMVG (0.60+/-0.13 versus -0.04+/-.13 seconds(-1) in the CM group, P<0.05). Results were similar at M12. In-scar accumulation of myotubes and SM were detected in all Tx animals up to M12, with co-expression of fast and slow isoforms of the myosin heavy chain (MHC) (30% of the fibers versus 0% in the normal skeletal muscle) and decreased collagen density (30+/-2% versus 73+/-3%, P<0.0001).
For up to 1 year, Tx of SM limits postinfarction EF deterioration and improves systolic scar function through colonization of fibrosis by skeletal muscle cells with expression of both MHC isoforms, which may confer to the graft the ability to withstand a cardiac-type workload.
Post-procedure residual ischemia is associated with worse prognosis in patients with coronary artery diasease (CAD).
We evaluated whether autologous bone marrow-derived cells (BMC) contribute to ...additional reduction in regional stress-induced myocardial ischemia (SIMI) in patients undergoing incomplete coronary artery bypass graft surgery (CABG).
In a double-blind, randomized, placebo-controlled trial, we enrolled 143 patients (82% men, 58 ± 11 years) with stable CAD and not candidates for complete CABG. They received 100 million BMC (
= 77) or placebo (
= 66) injected into ischemic non-revascularized segments during CABG. The primary outcome was improvement on SIMI quantified as the area at risk in injected segments assessed by cardiovascular magnetic resonance (CMR) 1, 6, and 12 months after CABG.
The reduction in global SIMI after CABG was comparable (
= 0.491) in both groups indicating sustained beneficial effects of the surgical procedure over 12 month period. In contrast, we observed additional improvement in regional SIMI in BMC treated group (
= 0.047). Baseline regional SIMI values were comparable 18.5 (16.2-21.0) vs. 18.5 (16.5-20.7) and reached the lowest values at 1 month 9.74 (8.25; 11.49) vs. 12.69 (10.84; 14.85) for BMC and placebo groups, respectively. The ischemia's improvement from baseline represented a 50% difference in regional SIMI in favor of the BMC transplanted group at 30 days. We found no differences in clinical and LVEF% between groups during the 12 month follow-up period. The 1 month rate of major adverse cerebral and cardiovascular events (MACCE) (
= 0.34) and all-cause mortality (
= 0.08) did not differ between groups 1 month post intervention.
We provided evidence that BMC leads to additional reduction in regional SIMI in chronic ischemic patients when injected in segments not subjected to direct surgical revascularization. This adjuvant therapy deserves further assessment in patients with advanced CAD especially in those with microcirculation dysfunction.
https://clinicaltrials.gov/, identifier NCT01727063.
Most transplanted organs are obtained from brain-dead donors. Inflammation results in a higher rate of rejection.
The objective of this animal model of brain death (BD) was to evaluate the effect of ...the progressive institution of volume expansion, norepinephrine, and combined hormone therapy on clinical, laboratory, and histological aspects.
Twenty rabbits were divided: A (control), B (induction of BD + infusion of crystalloid), C (BD + infusion of crystalloid and noradrenaline (NA)), and D (BD + infusion of crystalloid + vasopressin + levothyroxine + methylprednisolone + NA). The animals were monitored for four hours with consecutives analysis of vital signs and blood samples. The organs were evaluated by a pathologist.
In Group D, we observed fewer number and lesser volume of infusions (
= 0.032/0.014) when compared with groups B and C. Mean arterial pressure levels were higher in group D when compared with group B (
= 0.008). Group D had better glycemic control when compared with group C (
= 0.016). Sodium values were elevated in group B in relation to groups C and D (
= 0.021). In Group D, the organ perfusion was better.
The optimized strategy of management of BD animals is associated with better hemodynamic, glycemic, and natremia control, besides reducing early signs of ischemia.
Background: Tracheal lesions are pathologies derived from the most diverse insults that can result in a fatal outcome. Despite the number of techniques designed for the treatment, a limiting factor ...is the extent of the extraction. Therefore, strategies with biomaterials can restructure tissues and maintain the organ’s functionality, like decellularized Wharton’s jelly (WJ) as a scaffold. The aim is to analyze the capacity of tracheal tissue regeneration after the implantation of decellularized WJ in rabbits submitted to a tracheal defect. Methods: An in vivo experimental study was undertaken using twenty rabbits separated into two groups (n = 10). Group 1 submitted to a tracheal defect, group 2 tracheal defect, and implantation of decellularized WJ. The analyses were performed 30 days after surgery through immunohistochemistry. Results: Inner tracheal area diameter (p = 0.643) didn’t show significance. Collagen type I, III, and Aggrecan highlighted no significant difference between the groups (both collagens with p = 0.445 and the Aggrecan p = 0.4). Conclusion: The scaffold appears to fit as a heterologous implant and did not trigger reactions such as rejection or extrusion of the material into the recipient. However, these results suggested that although the WJ matrix presents several characteristics as a biomaterial for tissue regeneration, it did not display histopathological benefits in trachea tissue regeneration.
Recent studies have suggested that therapies with stem cells and amniotic membrane can modulate the inflammation following an ischemic injury in the heart. This study evaluated the effects of ...bone-marrow mononuclear cells (BMMC) and acellular human amniotic membrane (AHAM) on cardiac function and NLRP3 complex in a rat model of heart failure.On the 30th day,the echocardiographic showed improvements on ejection fraction and decreased pathological ventricular remodeling on BMMC and AHAM groups.Oxidative stress analysis was similar between the three groups,and the NLRP3 inflammasome activity were not decreased with the therapeutic use of both BMMC and AHAM,in comparison to the control group.
Wound healing is a complex process of repair that involves the interaction between different cell types and involves coordinated interactions between intracellular and extracellular signaling. Bone ...Marrow Mesenchymal Stem Cells (BMSCs) based and acellular amniotic membrane (AM) therapeutic strategies with the potential for treatment and regeneration of tissue. We aimed to evaluate the involvement of paracrine effects in tissue repair after the flap skin lesion rat model. In the full-thickness flap skin experiment of forty Wistar rats: A total of 40 male Wistar rats were randomized into four groups: group I: control (C; n = 10), with full-thickness lesions on the back, without (BMSCs) or AM (n = 10); group II: injected (BMSCs; n = 10); group III: covered by AM; group IV-injected (AM + BMSCs; n = 10). Cytokine levels, IL-1, and IL-10 assay kits, superoxide dismutase (SOD), glutathione reductase (GRs) and carbonyl activity levels were measured by ELISA 28th day, and TGF-β was evaluated by immunohistochemical, the expression collagen expression was evaluated by Picrosirius staining. Our results showed that the IL-1 interleukin was higher in the control group, and the IL-10 presented a higher mean when compared to the control group. The groups with BMSCs and AM showed the lowest expression levels of TGF-β. SOD, GRs, and carbonyl activity analysis showed a predominance in groups that received treatment from 80%. The collagen fiber type I was predominant in all groups; however, the AM + BMSCs group obtained a higher average when compared to the control group. Our findings suggest that the AM+ BMSCs promote skin wound healing, probably owing to their paracrine effect attributed to the promotion of new collagen for tissue repair.
Background: Tracheal grafts have been investigated for over a century, aiming to replace various lesions. However, tracheal reconstruction surgery remains a challenge, primarily due to anatomical ...considerations, intraoperative airway management, the technical complexity of reconstruction, and the potential postoperative morbidity and mortality. Due to research development, the amniotic membrane (AM) and Wharton’s Jelly (WJ) arise as alternatives within the new set of therapeutic alternatives. These structures hold significant therapeutic potential for tracheal defects. This study analyzed the capacity of tracheal tissue regeneration after 60 days of decellularized WJ and AM implantation in rabbits submitted to conventional tracheostomy. Methods: An in vivo experimental study was carried out using thirty rabbits separated into three groups (Control, AM, and WJ) (n = 10). The analyses were performed 60 days after surgery through immunohistochemistry. Results: Different immunomarkers related to scar regeneration, such as aggrecan, TGF-β1, and α-SMA, were analyzed. However, they highlighted no significant difference between the groups. Collagen type I, III, and Aggrecan also showed no significant difference between the groups. Conclusions: Both scaffolds appeared to be excellent frameworks for tissue engineering, presenting biocompatibility and a desirable microenvironment for cell survival; however, they did not display histopathological benefits in trachea tissue regeneration.
Objective. Achilles tendon pathologies occur frequently and have a significant socioeconomic impact. Currently, there is no evidence on the best treatment for these pathologies. Cell therapy has been ...studied in several animal models, and encouraging results have been observed with respect to tissue regeneration. This study is aimed at evaluating the functional and histological effects of bone marrow stem cell or platelet-rich plasma implantation compared to eccentric training in the treatment of Achilles tendinopathy in rats. Methods. Fourty-one male Wistar rats received collagenase injections into their bilateral Achilles tendons (collagenase-induced tendinopathy model). The rats were randomly divided into four groups: stem cells (SC), platelet-rich plasma (PRP), stem cells+platelet-rich plasma (SC+PRP), and control (eccentric training (ET)). After 4 weeks, the Achilles tendons were excised and subjected to biomechanical and histological analyses (Sirius red and hematoxylin-eosin staining). Results. Biomechanical assessments revealed no differences among the groups in ultimate tensile strength or yield strength of the tendons (p=0.157), but there were significant differences in the elastic modulus (MPa; p=0.044) and maximum tensile deformation (p=0.005). The PRP group showed the greatest maximum deformation, and the SC group showed the highest Young’s modulus (elasticity) measurement. In histological analysis (hematoxylin-eosin and Sirius red staining), there were no differences among the groups. Conclusion. PRP and SC+PRP yielded better biomechanical results than eccentric training, showing that these treatments offer better tend function outcomes. This theoretical rationale for the belief that cell therapies can serve as viable alternatives to current treatments chronic fibrotic opens the door for opportunities to continue this research.
A perfect graft for wound care must be readily available without affecting the immune response, covering and protecting the wound bed. Considering previous studies have already established the use of ...hyaluronic acid (HA) for the treatment of wounds but the data presented on the amniotic membrane (AM) and its promising effects on healing still requires further investigation, this study aimed to evaluate the effects of the application of a decellularized amniotic membrane solubilized with hyaluronic acid on the healing process of cutaneous wounds on the 7th and 14th day, to evaluate the evolution of the wound and the inflammatory phases in these two times. Cutaneous lesions were excised from the dorsal region and 96 Wistar rats were divided into four groups: I–Excisional wound (EW); II–EW + AM; III–EW + HA; IV–EW + AM + HA. The present study demonstrated that the proposed combined therapy favors the tissue repair process of the epithelial lesion. Results showed a reduction in pro-inflammatory cytokines, an increase in anti-inflammatory cytokines, an increase in TGF-β, and attenuation of oxidative stress, reducing the acute inflammatory response and promoting the beginning of tissue repair. We concluded that the proposed therapies accelerated the inflammatory process with anticipation of the repair phase.
Graphical Abstract
The primary aim of this study was to investigate muscle metabolism in stroke survivors through measurements of the respiratory exchange ratio and rates of fat and carbohydrate oxidation in relation ...to total energy expenditure at preferred walking speed during treadmill and overground walking. The secondary objective was to investigate whether the energy source used during walking influences the daily physical activity pattern and fatigue of post-stroke individuals.
The sample comprised 28 stroke participants and 10 non-disabled, healthy controls. Measurements of oxygen consumption and carbon dioxide production were recorded. Participants wore a uniaxial accelerometer (activPAL™) over 4 days as an estimate of daily physical activity. Measurements of Human Activity Profile and Neurological Fatigue Index for stroke were documented.
Carbohydrate oxidation accounted for the majority of fuel oxidation at preferred walking speed in the stroke group (55.86% vs 47.29% during tread-mill walking and 66.13% vs 50.15% during overground walking). Stroke patients who had higher levels of carbohydrate oxidation reached a lower score in the Human Activity Profile survey, had fewer steps screened by activPAL data (4,422 vs 6,692 steps/day) and higher fatigue index.
Carbohydrate oxidation accounted for the majority of fuel oxidation at the preferred walking speed in post-stroke individuals. The increased carbohydrate utilization recorded at preferred walking speed may have influenced the physical activity profile.
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