This review aimed to summarize the recent advances and challenges in the field of regenerative therapies for lumbar disc degeneration. The current first-line treatment options for symptomatic lumbar disc degeneration cannot modify the disease process or restore the normal structure, composition, and biomechanical function of the degenerated discs. Cell-based therapies tailored to facilitate intervertebral disc (IVD) regeneration have been developed to restore the IVD extracellular matrix or mitigate inflammatory conditions. Human clinical trials on Mesenchymal Stem Cells (MSCs) have reported promising outcomes exhibited by MSCs in reducing pain and improving function. Nucleus pulposus (NP) cells possess unique regenerative capacities. Biomaterials aimed at NP replacement in IVD regeneration, comprising synthetic and biological materials, aim to restore disc height and segmental stability without compromising the annulus fibrosus. Similarly, composite IVD replacements that combine various biomaterial strategies to mimic the native disc structure, including organized annulus fibrosus and NP components, have shown promise. Furthermore, preclinical studies on regenerative medicine therapies that utilize cells, biomaterials, growth factors, platelet-rich plasma (PRP), and biological agents have demonstrated their promise in repairing degenerated lumbar discs. However, these therapies are associated with significant limitations and challenges that hinder their clinical translation. Thus, further studies must be conducted to address these challenges.

UNASSIGNED: Bone marrow aspirate (BMA) intra-articular injection is a minimally invasive orthobiologic treatment option for osteoarthritis (OA). Hip OA affects a significant portion of the population and has a paucity of data surrounding orthobiologic treatments. The primary objective of this study was to delineate the clinical impact of bone marrow aspirate intra-articular injections on decreasing pain and improving function in patients with hip OA.
UNASSIGNED: A single-center, retrospective analysis of thirty-one patients, aged 32 to 83 (62.4 ​± ​16.5), with Kellgren-Lawrence (KL) Hip OA grading of 2-4 (mean 2.9 ​± ​0.7), who underwent intra-articular bone marrow aspirate injection into the hip and were followed for twelve months. Evaluation was at baseline, 12 weeks, 6 months, and 12 months using the Numerical Rating Scale (NRS) for pain and the Hip Disability and Osteoarthritis Outcome Score Jr (HOOS-Jr) for function. The proportion of responders, as defined by a ≥50% reduction in NRS pain score, was assessed at 12 weeks, 6 months and 12 months.
UNASSIGNED: At 6 and 12 months follow-up, there was a statistically significant improvement in NRS scores (P ​< ​0.05). Stratifying by KL grade, subjects with KL grades 2 and 3 experienced statistically significant improvement in NRS scores at 6 and 12 months. Patients with KL grade 4 showed significant improvement in pain at 12 months. Forty-two percent of patients at 6 months and 61% at 12 months reported ≥50% reduction in pain. When stratifying by KL grade, 80% and 71% of KL2 and KL3 grades respectively were responders by 12 months. Patients experienced statistically significant improvement in HOOS-Jr scores at 6 and 12 months.
UNASSIGNED: In patient with mild, moderate, and severe hip OA, BMA may be an alternative treatment that improves pain and function in patients for as long as 12 months. In addition, BMA may also be an effective, lower cost option to more expensive BMAC preparations.

Central nervous system (CNS) injuries and neurodegenerative diseases have markedly poor prognoses and can result in permanent dysfunction due to the general inability of CNS neurons to regenerate. Differentiation of transplanted stem cells has emerged as a therapeutic avenue to regenerate tissue architecture in damaged areas. Electrical stimulation is a promising approach for directing the differentiation outcomes and pattern of outgrowth of transplanted stem cells, however traditional inorganic bio-electrodes can induce adverse effects such as inflammation. This study demonstrates the implementation of two organic thin films, a polymer/reduced graphene oxide nanocomposite (P(rGO)) and PEDOT:PSS, that have favorable properties for implementation as conductive materials for electrical stimulation, as well as an inorganic indium tin oxide (ITO) conductive film. Transcriptomic analysis reveals that electrical stimulation improves neuronal differentiation of SH-SY5Y cells on all three films, with the greatest effect for P(rGO). Unique material- and electrical stimuli-mediated effects are observed, associated with differentiation, cell-substrate adhesion, and translation. The work demonstrates that P(rGO) and PEDOT:PSS are highly promising organic materials for the development of biocompatible, conductive scaffolds that will enhance electrically-aided stem cell therapeutics for CNS injuries and neurodegenerative diseases.

Extracellular vesicles (EVs) are vital for cell-to-cell communication, transferring proteins, lipids, and nucleic acids in various physiological and pathological processes. They play crucial roles in immune modulation and tissue regeneration but are also involved in pathogenic conditions like inflammation and degenerative disorders. EVs have heterogeneous populations and cargo, with numerous subpopulations currently under investigations. EV therapy shows promise in stimulating tissue repair and serving as a drug delivery vehicle, offering advantages over cell therapy, such as ease of engineering and minimal risk of tumorigenesis. However, challenges remain, including inconsistent nomenclature, complex characterization, and underdeveloped large-scale production protocols. This review highlights the recent advances and significance of EVs heterogeneity, emphasizing the need for a better understanding of their roles in disease pathologies to develop tailored EV therapies for clinical applications in neurological disorders.

Surgical procedures on large skin defects can be challenging in the short term due to the size of the lesion, infection, and tissue defect. A regenerative therapy for skin wounds has been applied to promote the healing process. An 8-month-old, Korean domestic short-haired female cat, weighing 3 kg, was rescued with extensive defects on the right flank to right inguinal region caused by bite wounds. In this case, amniotic membranes and adipose-derived mesenchymal stem cells were used as the regenerative therapy to treat the large skin defect rather than a surgical intervention alone. To the best of our knowledge, this is the first report of a case with of a large skin defect treated by applying allogeneic amniotic membranes and allogeneic mesenchymal stem cells to a cat.

The spatial arrangement of variant phenotypes during stem cell division plays a crucial role in the self-organization of cell tissues. The patterns observed in these cellular assemblies, where multiple phenotypes vie for space and resources, are largely influenced by a mixture of different diffusible chemical signals. This complex process is carried out within a chronological framework of interplaying intracellular and intercellular events. This includes receiving external stimulants, whether secreted by other individuals or provided by the environment, interpreting these environmental signals, and incorporating the information to designate cell fate. Here, given two distinct signaling patterns generated by Turing systems, we investigated the spatial distribution of differentiating cells that use these signals as external cues for modifying the production rates. By proposing a computational map, we show that there is a correspondence between the multiple signaling and developmental cellular patterns. In other words, the model provides an appropriate prediction for the final structure of the differentiated cells in a multi-signal, multi-cell environment. Conversely, when a final snapshot of cellular patterns is given, our algorithm can partially identify the signaling patterns that influenced the formation of the cellular structure, provided that the governing dynamic of the signaling patterns is already known.

BACKGROUND: Spinal cord injury (SCI) is a devastating injury and remains one of the largest medical and social burdens because of its intractable nature. According to the recent advances in stem cell biology, the possibility of spinal cord regeneration and functional restoration has been suggested by introducing appropriate stem cells. Multilineage-differentiating stress enduring (Muse) cells are a type of nontumorigenic endogenous reparative stem cell. The positive results of Muse cell transplantation for SCI was shown previously. As a first step for clinical application in human SCI, we conducted a clinical trial aiming to confirm the safety and feasibility of intravenously injected donor-Muse cells.
METHODS: The study design of the current trial was a prospective, multicenter, nonrandomized, nonblinded, single-arm study. The clinical trial registration number was JRCT1080224764. Patients with a cervical SCI with a neurological level of injury C4 to C7 with the severity of modified Frankel classification B1 and B2 were included. A primary endpoint was set for safety and feasibility. Our protocol was approved by the PMDA, and the trial was funded by the Life Science Institute, Tokyo, Japan. The present clinical trial recruited 10 participants (8 males and 2 females) with an average age of 49.3 ± 21.2 years old. All 10 participants received a single dose of allogenic CL2020 (a total of 15 × 106 cells, 2.1-2.7 × 105 cells/kg of body weight), which is a Muse cell-based product produced from human mesenchymal stem cells, by an intravenous drip.
RESULTS: There were two reported severe adverse events, both of which were determined to have no causal relationship with Muse cell treatment. The change in the ISNCSCI motor score, the activity of daily living and quality of life scores showed statistically significant improvements compared to those data at the time of CL2020 administration.
CONCLUSIONS: In the present trial, no safety concerns were identified, and Muse cell product transplantation demonstrated good tolerability. Future clinical trials with appropriate study designs incorporating a control arm will clarify the definitive efficacy of single-dose allogenic Muse cell treatment with intravenous administration to treat SCI.
BACKGROUND: jRCT, JRCT1080224764. Registered 03 July 2019, https://jrct.niph.go.jp/latest-detail/jRCT1080224764 .

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UNASSIGNED: Loxoscelism refers to a set of clinical manifestations caused by the bite of spiders from the Loxosceles genus. The classic clinical symptoms are characterized by an intense inflammatory reaction at the bite site followed by local necrosis and can be classified as cutaneous loxoscelism. This cutaneous form presents difficult healing, and the proposed treatments are not specific or effective. This study aimed to evaluate the protective effect of mesenchymal stromal cells-derived secretome on dermonecrosis induced by Loxosceles intermedia spider venom in rabbits.
UNASSIGNED: Sixteen rabbits were distributed into four groups (n = 4). Except for group 1 (G1), which received only PBS, the other three groups (G2, G3, and G4) were initially challenged with 10 μg of L. intermedia venom, diluted in 100 μL of NaCl 0.9%, by intradermic injection in the interscapular region. Thirty minutes after the challenge all groups were treated with secretome, except for group 2. Group 1 (G1-control group) received intradermal injection (ID) of 60 μg of secretome in 0.15 M PBS; Group 2 (G2) received 0.9% NaCl via ID; Group 3 (G3) received 60 μg of secretome, via ID and Group 4 (G4), received 60 μg of secretome by intravenous route. Rabbits were evaluated daily and after 15 days were euthanized, necropsied and skin samples around the necrotic lesions were collected for histological analysis.
UNASSIGNED: Rabbits of G1 did not present edema, erythema, hemorrhagic halo, or necrosis. In animals from G2, G3, and G4, edema appeared after 6h. However, minor edema was observed in the animals of G2 and G3. Hemorrhagic halo was observed in animals, six hours and three days after, on G2, G3, and G4. Macroscopically, in G4, only one animal out of four had a lesion that evolved into a dermonecrotic wound. No changes were observed in the skin of the animals of G1, by microscopic evaluation. All animals challenged with L. intermedia venom showed similar alterations, such as necrosis and heterophilic infiltration. However, animals from G4 showed fibroblast activation, early development of connective tissue, neovascularization, and tissue re-epithelialization, indicating a more prominent healing process.
UNASSIGNED: These results suggest that secretome from mesenchymal stromal cells cultured in a xeno-free and human component-free culture media can be promising to treat dermonecrosis caused after Loxosceles spiders bite envenoming.