Archive for June 2025
Stem Cell–Derived, Fully Differentiated Islets for Type 1 Diabetes
Results
A total of 14 participants (2 in part A and 12 in parts B and C) completed at least 12 months of follow-up and were included in the analyses. C-peptide was undetectable at baseline in all 14 participants. After zimislecel infusion, all the participants had engraftment and islet function, as evidenced by the detection of C-peptide. Neutropenia was the most common serious adverse event, occurring in 3 participants.
Two deaths occurred — one caused by cryptococcal meningitis and one by severe dementia with agitation owing to the progression of preexisting neurocognitive impairment. All 12 participants in parts B and C were free of severe hypoglycemic events and had a glycated hemoglobin level of less than 7%; these participants spent more than 70% of the time in the target glucose range (70 to 180 mg per deciliter). Ten of the 12 participants (83%)
Advances in Stem Cell Therapies for Rotator Cuff Injuries
Rotator cuff injury is a common upper extremity musculoskeletal disease that may lead to persistent pain and functional impairment. Despite the clinical outcomes of the surgical procedures being satisfactory, the repair of the rotator cuff remains problematic, such as through failure of healing, adhesion formation, and fatty infiltration. Stem cells have high proliferation, strong paracrine action, and multiple differentiation potential, which promote tendon remodeling and fibrocartilage formation and increase biomechanical strength. Additionally, stem cell-derived extracellular vesicles (EVs) can increase collagen synthesi and inhibit inflammation and adhesion formation by carrying regulatory proteins and microRNAs. Therefore, stem cell-based therapy is a promising therapeutic strategy that has great potential for rotator cuff healing. In this review, we summarize the advances of stem cells and stem cell-derived EVs in rotator cuff repair and highlight the underlying mechanism of stem cells and stem cell-derived EVs and biomaterial delivery systems. Future studies need to explore stem cell therapy in combination with cellular factors, gene therapy, and novel biomaterial delivery systems.
Stem cell therapies in tendon-bone healing
Abstract
Tendon-bone insertion injuries such as rotator cuff and anterior cruciate ligament injuries are currently highly common and severe. The key method of treating this kind of injury is the reconstruction operation. The success of this reconstructive process depends on the ability of the graft to incorporate into the bone. Recently, there has been substantial discussion about how to enhance the integration of tendon and bone through biological methods. Stem cells like bone marrow mesenchymal stem cells (MSCs), tendon stem/progenitor cells, synovium-derived MSCs, adipose-derived stem cells, or periosteum-derived periosteal stem cells can self-regenerate and potentially differentiate into different cell types, which have been widely used in tissue repair and regeneration. Thus, we concentrate in this review on the current circumstances of tendon-bone healing using stem cell therapy.
Intratendinous Injection of AutologousAdipose Tissue-Derived MesenchymalStem Cells for the Treatment of RotatorCuff Disease: A First-In-Human Trial
ABSTRACT
Despite relatively good results of current symptomatictreatments for rotator cuff disease, there has been an unmetneed for fundamental treatments to halt or reverse the progressof disease. The purpose of this study was to assess the safety andefficacy of intratendinous injection of autologous adiposetissue-derived mesenchymal stem cells (AD MSCs) in patientswith rotator cuff disease. The first part of the study consists ofthree dose-escalation cohorts; the low- (1.0 × 10 cells), mid- (5.0× 10), and high-dose (1.0 × 10) groups with three patients eachfor the evaluation of the safety and tolerability. The second partincluded nine patients receiving the high-dose for theevaluation of the exploratory efficacy. The primary outcomeswere the safety and the shoulder pain and disability index(SPADI). Secondary outcomes included clinical, radiological, andarthroscopic evaluations. Twenty patients were enrolled in thestudy, and two patients were excluded. Intratendinous injectionof AD MSCs was not associated with adverse events. Itsignificantly decreased the SPADI scores by 80% and 77% in themid- and high-dose groups, respectively. Shoulder pain wassignificantly alleviated by 71% in the high-dose group. Magneticresonance imaging examination showed that volume of thebursal-side defect significantly decreased by 90% in the high-dose group. Arthroscopic examination demonstrated thatvolume of the articular- and bursal-side defects decreased by83% and 90% in the mid- and high-dose groups, respectively.Intratendinous injection of autologous AD MSCs in patient witha partial-thickness rotator cuff tear did not cause adverse events,but improved shoulder function, and relieved pain throughregeneration of rotator cuff tendon.
Mesenchymal Stem Cells From a Hypoxic Culture Can Improve Rotator Cuff Tear Repair
Abstract
A rotator cuff tear is an age-related common cause of pain and disability. Studies including our previously published ones have demonstrated that mesenchymal stem cells cultured under hypoxic conditions [hypoxic multipotent stromal cells (MSCs)] facilitate the retention of transplanted cells and promote wound healing. However, there are very few, if any, reports targeting the punctured supraspinatus tendons to create more or equally serous wounds as age-related tears of rotator cuff. It remains to be determined whether transplantation of bone-marrow-derived hypoxic MSCs into the punctured supraspinatus tendon improves tendon repair and, when combined with ultrasound-guided delivery, could be used for future clinical applications. In this study, we used a total of 33 Sprague-Dawley rats in different groups for normal no-punched control, hypoxic MSC treatment, nontreated vehicle control, and MSC preparation, and then evaluated treatment outcomes by biomechanical testing and histological analysis. We found that the ultimate failure load of the hypoxic MSC-treated group was close to that of the normal tendon and significantly greater than that of the nontreated vehicle control group. In vivo tracking of cells labeled with superparamagnetic iron oxide (SPIO) nanoparticles revealed an enhanced retention of transplanted cells at the tear site. Our study demonstrates that hypoxic MSCs improve rotator cuff tear repair in a rat model.
Phase I trial of hES cell-derived dopaminergic neurons for Parkinson’s disease
Parkinson’s disease is a progressive neurodegenerative condition with a considerable health and economic burden1. It is characterized by the loss of midbrain dopaminergic neurons and a diminished response to symptomatic medical or surgical therapy as the disease progresses. Cell therapy aims to replenish lost dopaminergic neurons and their striatal projections by intrastriatal grafting. Here, we report the results of an open-label phase I clinical trial (NCT04802733) of an investigational cryopreserved, off-the-shelf dopaminergic neuron progenitor cell product (bemdaneprocel) derived from human embryonic stem (hES) cells and grafted bilaterally into the putamen of patients with Parkinson’s disease. Twelve patients were enrolled sequentially in two cohorts—a low-dose (0.9 million cells, n = 5) and a high-dose (2.7 million cells, n = 7) cohort—and all of the participants received one year of immunosuppression. The trial achieved its primary objectives of safety and tolerability one year after transplantation, with no adverse events related to the cell product. At 18 months after grafting, putaminal 18Fluoro-DOPA positron emission tomography uptake increased, indicating graft survival. Secondary and exploratory clinical outcomes showed improvement or stability, including improvement in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III OFF scores by an average of 23 points in the high-dose cohort. There were no graft-induced dyskinesias. These data demonstrate safety and support future definitive clinical studies.
Repeated Intravenous Administration of Mesenchymal Stromal Cells Produces Cumulative Beneficial Effects in Chronic Ischemic Cardiomyopathy
Cell therapy is a potentially useful approach to treating heart failure (HF) secondary to chronic ischemic cardiomyopathy (ischemic HF). Despite controversy, the preclinical data in the field of cell therapy are clear: Although transplanted cells do not regenerate cardiomyocytes, preclinical studies have consistently shown that they improve cardiac performance. Bone marrow–derived mesenchymal stromal cells (MSCs) are among the most promising cell types in the preclinical arena1 and for patients with ischemic HF.
The field of cell therapy is evolving rapidly. The fundamental shift has been the recognition that all cell types fail to engraft in the heart and instead work via paracrine mechanisms. This concept has 2 corollaries: (1) because transplanted cells do not persist in the heart for more than a few weeks, giving repeated doses seems logical; and (2) because cells work by releasing factors in the environment, intravenous (IV) therapy may also be effective by enabling systemic release of these factors.