Search Results (11)

Coronary artery disease (CAD) remains a leading cause of global morbidity and mortality despite advances in medical and interventional therapies. Mesenchymal stem cell (MSC) therapy has emerged as a promising regenerative approach for patients with refractory or non-revascularizable CAD. MSCs exhibit unique immunomodulatory, pro-angiogenic, and anti-fibrotic properties, primarily through paracrine mechanisms involving the secretion of cytokines, growth factors, and exosomal microRNAs. Clinical and preclinical studies have demonstrated improvements in myocardial perfusion, left ventricular ejection fraction (LVEF), and functional capacity following MSC-based interventions, particularly in patients with low baseline LVEF and heightened inflammation. Various MSC sources—including bone marrow, adipose tissue, and umbilical cord—offer distinct advantages, while delivery strategies such as intracoronary, intramyocardial, intravenous, and subcutaneous administration impact cell retention and efficacy. Advances in genetic modification, hypoxic preconditioning, and exosome-based therapies aim to enhance MSC survival and therapeutic potency. However, challenges persist regarding cell engraftment, cryopreservation effects, and inter-patient variability. Moving toward precision cell therapy, future approaches may involve stratifying patients by inflammatory status, ischemic burden, and comorbidities to optimize treatment outcomes. MSCs may not yet replace conventional therapies but are increasingly positioned to complement them within a personalized, regenerative framework for CAD management. Full article

Introduction: Mastectomy skin necrosis (MSN) is a common complication occurring in up to 50% of patients. In patients with risk factors for poor wound healing such as immunosuppression, prior radiotherapy (XRT), and high body mass index (BMI > 30.0), this number is even higher. MSN can lead to infection, loss of reconstruction, poorer aesthetics, and most ominously, delay in adjuvant cancer therapy. Instead of forgoing reconstruction in these patients, adjunctive therapies to optimize wound healing are necessary. The purpose of this study is to introduce the use of cryopreserved umbilical tissue (vCUT) as an adjunct therapy for high-risk-wound-healing immediate breast reconstruction (IBR) patients. Methods: All patients who underwent breast reconstruction with vCUT as an adjunctive therapy were identified and retrospectively analyzed. Results: Seven patients who underwent breast reconstruction with vCUT placement were identified. These patients had risk factors for delayed healing, such as obesity, immunosuppression, and/or prior XRT. The mean post-operative follow-up was 252 days (range 183–287). Four out of seven patients demonstrated post-operative complications: two out of seven developed seromas, two out of seven developed wound dehiscence, two out of seven developed infection, two out of seven developed MSN, and two out of seven lost their reconstruction. Conclusion: As undergoing IBR leads to improved mental health and superior aesthetic outcomes, efforts to expand current indications for safe IBR to traditionally poorer reconstructive candidates are imperative. The results of this case series demonstrate vCUT as a promising novel adjunctive tool in the reconstructive surgeons’ armamentarium in managing the less ideal reconstructive breast candidate. Full article

Background: Osteoarthritis is a chronic disorder that affects the synovial joints by the progressive loss of articular cartilage. In the hip, the largest weight-bearing joint, the deterioration of articular cartilage and acetabular labrum can cause pain, diminishing the quality of life for patients. This study presents changes in reported pain scales from patients who received Wharton’s jelly applications to cartilage deterioration in the hip from the observational retrospective repository at Regenative Labs. Methods: Sixty-nine patients were selected based on inclusion criteria with patient-reported pain scales, including the Numeric Pain Rating Scale and the Western Ontario and McMaster University Osteoarthritis Index, collected at the initial application, 30, and 90-day follow-up visits. Thirteen patients received a second allograft application and had additional follow-up visits at 120 and 180 days. Results: Five of the six scales used showed a statistically significant improvement in average scores across the cohort. The greatest improvements were observed in the NPRS with a 31.36% improvement after 90 days and a 44.64% improvement for patients with two applications after 180 days. The minimal clinically important difference (MCID) was also calculated to determine the perceived value of care for each patient with 44.9% of patients exceeding the MCID and 78.3% reporting at least one level of improvement. Conclusions: The positive outcomes for the patients in this cohort suggest WJ to be a promising alternative care option for patients with structural tissue degeneration in the hip refractory to the current standard of care. Full article

Currently, there is no viable option for fertility preservation in prepubertal boys. Experimentally, controlled vitrification of testicular tissue has been evaluated and found to cause potential structural damage to the spermatogonial stem cell (SSC) niche during cryopreservation. In this report, we leveraged the regenerative effect of human umbilical cord-derived Mesenchymal stem cell exosomes (h-UCMSC-Exo) to protect against testicular damage from the cytotoxic effects of polychemotherapy (CTX). A chemotherapy-induced testicular dysfunctional model was established by CTX treatment with cyclophosphamide and Busulfan in vitro (human Sertoli cells) and in prepubescent mice. We assessed the effects of the exosomes by analyzing cell proliferation assays, molecular analysis, immunohistochemistry, body weight change, serum hormone levels, and fertility rate. Our data indicates the protective effect of h-UCMSC-Exo by preserving the SSC niche and preventing testicular damage in mice. Interestingly, mice that received multiple injections of h-UCMSC-Exo showed significantly higher fertility rates and serum testosterone levels (p < 0.01). Our study demonstrates that h-UCMSC-Exo can potentially be a novel fertility protection approach in prepubertal boys triaged for chemotherapy treatment. Full article

This Institutional Review Board (IRB)-approved retrospective observational protocol aims to report the safety and efficacy of birth tissue allografts applied in 38 patients with treatment-resistant sacroiliac (SI) joint pain. The research methodology consisted of an observational recording of the Numeric Pain Rating Scale (NPRS) and the Western Ontario and McMaster Universities Arthritis Index (WOMAC), which measure pain, stiffness, and physical function. No adverse events or adverse reactions were observed in the 38 patients. Statistically significant improvements in NPRS and WOMAC scores of the affected SI joint were reported after 90 days. The observational data suggests that Wharton’s jelly allograft applications are safe, minimally invasive, and efficacious. They may present an alternative to surgery for patients who fail conservative and procedural management of pain originating from chondral cartilage degeneration of the SI joint. Full article

The primary objective of this study is to report the initial efficacy data observed with the use of cryopreserved human umbilical tissue allografts for supplementation in patients with symptomatic degeneration of load-bearing articular cartilage in the knee joint. Our primary endpoints were pain, stiffness, and functional recovery scores. In this ongoing study, 55 participants (age 56–93 years) received a single Wharton’s jelly tissue allograft application. The study dose consisted of 150 mg of Wharton’s jelly allograft suspended in approximately 2 mL of sterile sodium chloride 0.9% solution (normal saline). Each study knee application was performed under ultrasound guidance in a physician’s office. The research methodology consisted of Numeric Pain Rating Scale (NPRS) scores and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subsection scores including pain, stiffness, and physical function. Study enrollment consisted of 55 patients followed for a post-application duration of 90 days. No adverse events or adverse reactions were reported. The results demonstrated statistically significant improvements of NPRS and WOMAC in initial versus 90-day examination. The data represent Wharton’s jelly tissue allograft applications are safe, non-surgical, and efficacious for patients with symptomatic osteoarthritis of the knee. Full article

To determine if knee pain subjects who received cryopreserved umbilical cord tissue (UCT) injected into knee joints experience less knee pain, better function, decreased physical limitations, and reduction of medications (opiates, NSAIDs, and acetaminophen) over a 24 week period, Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and medication usage data were recorded for 30 consenting human knee pain subjects receiving UCT at a single site in the United States. Subject profile information was gathered and analyzed to gain insight into the effects of age, sex, and BMI on improvement over time. Mean resting VAS scores and mean VAS scores with activity improved over 24 weeks (from 1.95 to 0.83 and from 6.28 to 2.87, respectively, p < 0.001). There was no strong evidence of a correlation between sex and VAS scores. There were statistically significant correlations for BMI vs. pre-injection VAS with activity scores and Age vs. pre-injection VAS with activity scores (r = 0.402, p = 0.028 and r = 0.434, p = 0.017, respectively). Mean WOMAC scores improved from 44.7 to 18.5 over 24 weeks (p < 0.001). 77.8% of patients who used medications at the beginning of the study reduced or eliminated medication use. The analysis demonstrates that injections with UCT decrease pain, improve physical function, and allow for less medication use for at least 24 weeks. Full article

Background: Ventilator-induced lung injury (VILI) frequently worsens acute respiratory distress syndrome (ARDS) severity. Human mesenchymal stem/stromal cells (MSCs) offer considerable therapeutic promise, but the key impediments of clinical translation stem from limitations due to cell source and availability, and concerns regarding the loss of efficacy following cryopreservation. These experiments compared the efficacy of umbilical-cord-derived MSCs (UC-MSCs), a readily available and homogenous tissue source, to the previously more widely utilised bone-marrow-derived MSCs (BM-MSCs). We assessed their capacity to limit inflammation, resolve injury and enhance repair in relevant lung mechanical stretch models, and the impact of cryopreservation on therapeutic efficacy. Methods: In series 1, confluent alveolar epithelial layers were subjected to cyclic mechanical stretch (22% equibiaxial strain) and wound injury, and the potential of the secretome from BM- and UC-derived MSCs to attenuate epithelial inflammation and cell death, and enhance wound repair was determined. In series 2, anesthetized rats underwent VILI, and later received, in a randomised manner, 1 × 10⁷ MSCs/kg intravenously, that were: (i) fresh BM-MSCs, (ii) fresh UC-MSCs or (iii) cryopreserved UC-MSCs. Control animals received a vehicle (PBS). The extent of the resolution of inflammation and injury, and repair was measured at 24 h. Results: Conditioned medium from BM-MSCs and UC-MSCs comparably decreased stretch-induced pulmonary epithelial inflammation and cell death. BM-MSCs and UC-MSCs comparably enhanced wound resolution. In animals subjected to VILI, both fresh BM-MSCs and UC-MSCs enhanced injury resolution and repair, while cryopreserved UC-MSCs comparably retained their efficacy. Conclusions: Cryopreserved UC-MSCs can reduce stretch-induced inflammation and cell death, enhance wound resolution, and enhance injury resolution and repair following VILI. Cryopreserved UC-MSCs represent a more abundant, cost-efficient, less variable and equally efficacious source of therapeutic MSC product. Full article

Objectives: Use of off-label tissue graft materials, such as acellular dermal matrix (ADM), for in utero repair of severe spina bifida (SB), where primary skin layer closure is not possible, is associated with poor neurological outcomes. The cryopreserved human umbilical cord (HUC) patch has regenerative, anti-inflammatory, and anti-scarring properties, and provides watertight SB repair. We tested the hypothesis that the HUC is a superior skin patch to ADM for reducing inflammation at the repair site and preserving spinal cord function. Methods: In timed-pregnant ewes with twins, on gestational day (GD) 75, spina bifida was created without a myelotomy (functional model). On GD 95, repair was performed using HUC vs. ADM patches (randomly assigned) by suturing them to the skin edges. Additionally, full thickness skin closure as a primary skin closure (PSC) served as a positive control. Delivery was performed on GD 140, followed by blinded to treatment neurological assessments of the lambs using the Texas Spinal Cord Injury Scale (TSCIS) for gait, proprioception, and nociception. Lambs without spina bifida were used as controls (CTL). Ex vivo magnetic resonance imaging of spines at the repair site were performed, followed by quantitative pathological assessments. Histological assessments (blinded) included Masson’s trichrome, and immunofluorescence for myeloperoxidase (MPO; neutrophils) and for reactive astrocytes (inflammation) by co-staining vimentin and GFAP. Results: The combined hind limbs’ TSCIS was significantly higher in the HUC group than in ADM and PSC groups, p = 0.007. Both ADM and PSC groups exhibited loss of proprioception and mild to moderate ataxia compared to controls. MRI showed increased pathological findings in the PSC group when compared to the HUC group, p = 0.045. Histologically, the meningeal layer was thickened (inflammation) by 2–3 fold in ADM and PSC groups when compared to HUC and CTL groups, p = 0.01. There was lower MPO positive cells in the HUC group than in the ADM group, p = 0.018. Posterior column astrocyte activation was increased in ADM and PSC lambs compared to HUC lambs, p = 0.03. Conclusion: The HUC as a skin patch for in utero spina bifida repair preserves spinal cord function by reducing underlying inflammation when compared to ADM. Full article

Mesenchymal stromal cells (MSCs) have a multimodal, immunomodulatory mechanism of action and are now in clinical trials for single organ and systemic sepsis. However, a number of practicalities around source, homogeneity and therapeutic window remain to be determined. Here, we utilised conditioned medium from CD362⁺-sorted umbilical cord-human MSCs (UC-hMSCs) for a series of in vitro anti-inflammatory assays and the cryopreserved MSCs themselves in a severe (Series 1) or moderate (Series 2+3) caecal ligation and puncture (CLP) rodent model. Surviving animals were assessed at 48 h post injury induction. MSCs improved human lung, colonic and kidney epithelial cell survival following cytokine activation. In severe systemic sepsis, MSCs administered at 30 min enhanced survival (Series 1), and reduced organ bacterial load. In moderate systemic sepsis (Series 2), MSCs were ineffective when delivered immediately or 24 h later. Of importance, MSCs delivered 4 h post induction of moderate sepsis (Series 3) were effective, improving serum lactate, enhancing bacterial clearance from tissues, reducing pro-inflammatory cytokine concentrations and increasing antimicrobial peptides in serum. While demonstrating benefit and immunomodulation in systemic sepsis, therapeutic efficacy may be limited to a specific point of disease onset, and repeat dosing, MSC enhancement or other contingencies may be necessary. Full article

Biofilm, a community of bacteria, is tolerant to antimicrobial agents and ubiquitous in chronic wounds. In a chronic DFU (Diabetic Foot Ulcers) clinical trial, the use of a human cryopreserved viable amniotic membrane (CVAM) resulted in a high rate of wound closure and reduction of wound-related infections. Our previous study demonstrated that CVAM possesses intrinsic antimicrobial activity against a spectrum of wound-associated bacteria under planktonic culture conditions. In this study, we evaluated the effect of CVAM and cryopreserved viable umbilical tissue (CVUT) on biofilm formation of S. aureus and P. aeruginosa, the two most prominent pathogens associated with chronic wounds. Firstly, we showed that, like CVAM, CVUT released antibacterial activity against multiple bacterial pathogens and the devitalization of CVUT reduced its antibacterial activity. The biofilm formation was then measured using a high throughput method and an ex vivo porcine dermal tissue model. We demonstrate that the formation of biofilm was significantly reduced in the presence of CVAM- or CVUT-derived conditioned media compared to control assay medium. The formation of P. aeruginosa biofilm on CVAM-conditioned medium saturated porcine dermal tissues was reduced 97% compared with the biofilm formation on the control medium saturated dermal tissues. The formation of S. auerus biofilm on CVUT-conditioned medium saturated dermal tissues was reduced 72% compared with the biofilm formation on the control tissues. This study is the first to show that human cryopreserved viable placental tissues release factors that inhibit biofilm formation. Our results provide an explanation for the in vivo observation of their ability to support wound healing. Full article