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Spinal cord injury (SCI) has limited treatment options for regaining function. Adipose-derived stem cells (ADSCs) show promise owing to their ability to differentiate into multiple cell types, promote nerve cell survival, and modulate inflammation. This review explores ADSC therapy for SCI, focusing on its potential for improving function, preclinical and early clinical trial progress, challenges, and future directions. Preclinical studies have demonstrated ADSC transplantation's effectiveness in promoting functional recovery, reducing cavity formation, and enhancing nerve regrowth and myelin repair. To improve ADSC efficacy, strategies including genetic modification and combination with rehabilitation are being explored. Early clinical trials have shown safety and feasibility, with some suggesting motor and sensory function improvements. Challenges remain for clinical translation, including optimizing cell survival and delivery, determining dosing, addressing tumor formation risks, and establishing standardized protocols. Future research should focus on overcoming these challenges and exploring the potential for combining ADSC therapy with other treatments, including rehabilitation and medication.
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Chronic wounds represent a significant global burden, afflicting millions with debilitating complications. Despite standard care, impaired healing persists due to factors like persistent inflammation and impaired tissue regeneration. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) offer an innovative regenerative medicine approach, delivering stem cell-derived therapeutic cargo in engineered nanoscale delivery systems. This review examines pioneering bioengineering strategies to engineer MSC-EVs into precision nanotherapeutics for chronic wounds. Emerging technologies like CRISPR gene editing, microfluidic manufacturing, and biomimetic delivery systems are highlighted for their potential to enhance MSC-EV targeting, optimize therapeutic cargo enrichment, and ensure consistent clinical-grade production. However, key hurdles remain, including batch variability, rigorous safety assessment for potential tumorigenicity, immunogenicity, and biodistribution profiling. Crucially, collaborative frameworks harmonizing regulatory science with bioengineering and patient advocacy hold the key to expediting global clinical translation. By overcoming these challenges, engineered MSC-EVs could catalyze a new era of off-the-shelf regenerative therapies, restoring hope and healing for millions afflicted by non-healing wounds.
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Gallbladder cancer (GBC) is an uncommon malignancy that is highly aggressive in the advanced stages. However, it rarely metastasizes to the mandible. Numb chin syndrome (NCS) is a rare neurological manifestation associated with various underlying causes, including occult primary cancers and distant metastases. It is often considered to be a significant indicator of malignancy, and thorough investigation is essential in the presence of unclear etiology. The current study reported on the case of a 69-year-old Japanese woman who presented with numbness and mild pain in the lower lip and chin area for three months. No other systemic symptoms were observed. Immunocytochemical examination revealed the presence of an adenocarcinoma and TNM staging as per the Union for International Cancer Control and the American Joint Committee on Cancer guidelines confirmed stage IVb GBC. Comprehensive full-body positron emission tomography-computed tomography examination using 18F-fluoro-2-deoxy-D-glucose revealed additional bone and soft-tissue metastases. Palliative chemotherapy and radiation treatment were initiated based on the advanced stage of disease at the time of diagnosis. However, the patient succumbed to multiple organ failure six months later. The simultaneous occurrence of GBC, mandibular metastasis and NCS is rare and associated with poor prognosis. Despite the widespread nature of the disease, it can often manifest as non-specific oral symptoms without any systemic indications. The current study emphasizes the critical importance of timely confirmatory testing for accurate diagnosis and initiation of appropriate management for such complex conditions.
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Metastatic colorectal carcinoma involving the maxilla is a rare phenomenon, and existing literature regarding the significance of perioperative oral function management (POM) in managing such cases is limited. In the present case report the clinical details of a 58-year-old male referred to the oral and maxillofacial department for POM. The patient had previously undergone segmental bowel resection due to stage IIIb colon cancer. A comprehensive approach encompassing a thorough medical history, meticulous physical examination, radiographic imaging and immunohistopathology was employed, and a definitive diagnosis of metastatic adenocarcinoma in the left maxillary gingiva originating from a colorectal carcinoma was reached. Additionally, concomitant metastases were detected in the lungs and liver. Despite the daunting prognosis associated with the metastases in the oral cavity, the patient's quality of life exhibited discernible improvements owing to the implementation of palliative care interventions. Notably, this interdisciplinary approach facilitated the patient's survival for over a year. The present case report strongly advocates for the prompt integration of POM in the surgical management of cancer patients with oral manifestations, which can optimize both the quality of life and overall survival.
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Despite significant advancements in therapeutic approaches, oral neoplasms remain formidable and lifethreatening conditions that affect a substantial number of individuals worldwide. Within oral malignancies, a subset of cancer stem cells (CSCs) represent a crucial population responsible for tumor initiation and progression. The identification of reliable markers for the detection and characterization of CSCs in solid tumors, particularly in the context of oral cancers, remains an ongoing challenge. Stagespecific embryonic antigen 3 (SSEA3), previously associated with mesenchymal stem cells and linked to the progression of breast neoplasms and poor prognosis, has yet to be comprehensively elucidated in the context of oral malignancies. The present study aimed to investigate the expression and properties of SSEA3 in 16 distinct subsets of human oral neoplastic cell lines, classified as either CD44 positive (+) or CD44 negative (). For the first time, SSEA3 was examined as an indicator of tumorigenicity and resistance to taxanederived chemotherapeutic agents. In the majority of oral neoplastic cell lines analyzed, SSEA3 was expressed in a small population of CD44(+) cells. Significantly, SSEA3(+) cells exhibited heightened proliferative activity and upregulated expression of genes associated with stem cells compared with SSEA3() cells. The aforementioned findings suggested that SSEA3 may contribute to the evolution and progression of oral malignancies by fostering tumor growth. Furthermore, SSEA3(+) cells displayed increased sensitivity to taxanebased pharmaceuticals, indicating the potential for SSEA3 to be a viable target in the treatment schema for oral cavity neoplasms. In conclusion, the present study provides novel insight into the role of SSEA3 in the progression and management of oral neoplasms, potentially paving the way for more effective therapeutic approaches.
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Neoplasias Bucais , Humanos , Antígenos Embrionários Estágio-Específicos , Neoplasias Bucais/tratamento farmacológico , Transformação Celular Neoplásica , Linhagem Celular Tumoral , Células-Tronco NeoplásicasRESUMO
Poland syndrome (PS), an uncommon congenital unilateral aplasia of chest wall muscles, may exhibit rare accompanying signs, such as axillary webbing or contractures. The existing literature on the specific management of axillary contractures is limited. In this report, we present the case of a 10-year-old girl with PS manifesting an axillary web containing a fibrous band, which was successfully surgically corrected by a double-opposing Z-plasty. Our surgical approach entailed a meticulous distinction between the deep fibrous band and the superficial cutaneous layer, guided by histopathological findings that indicated the presence of tendon-like tissue, ultimately yielding excellent outcomes. This report will help expand knowledge by highlighting the unique manifestation of PS and emphasizing the importance of employing appropriate treatment approaches. Moreover, addressing both tendon and skin components is essential for optimal contracture release in PS.
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Rheumatoid arthritis (RA) is a highly prevalent, chronic, and progressive autoimmune disorder primarily affecting joints and muscles. The associated inflammation, pain, and motor restriction negatively impact patient quality of life (QOL) and can even contribute to premature mortality. Further, conventional treatments such as antiinflammatory drugs are only symptomatic. Substantial progress has been made on elucidating the etiopathology of overt RA, in particular the contributions of innate and adaptive immune system dysfunction to chronic inflammation. Although the precise mechanisms underlying onset and progression remain elusive, the discovery of new drug targets, early diagnosis, and new targeted treatments have greatly improved the prognosis and QOL of patients with RA. However, a sizable proportion of patients develop severe adverse effects, exhibit poor responses, or cannot tolerate long-term use of these drugs, necessitating more effective and safer therapeutic alternatives. Mounting preclinical and clinical evidence suggests that the transplantation of multipotent adult stem cells such as mesenchymal stromal/stem cells is a safe and effective treatment strategy for controlling chronic inflammation and promoting tissue regeneration in patients with intractable diseases, including RA. This review describes the current status of MSC-based therapies for RA as well as the opportunities and challenges to broader clinical application.
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Artrite Reumatoide , Doenças Autoimunes , Células-Tronco Mesenquimais , Humanos , Qualidade de Vida , Células-Tronco Mesenquimais/patologia , InflamaçãoRESUMO
The mortality rate of oral cancer has not improved over the past three decades despite remarkable advances in cancer therapies. Oral cancers contain a subpopulation of cancer stem cells (CSCs) that share characteristics associated with normal stem cells, including self-renewal and multi-differentiation potential. CSCs are tumorigenic, play a critical role in cancer infiltration, recurrence, and distant metastasis, and significantly contribute to drug resistance to current therapeutic strategies, including immunotherapy. Cytotoxic CD8+ T lymphocytes (CTLs) are key immune cells that effectively recognize peptide antigens presented by the major histocompatibility complex class I molecules. Increasing evidence suggests that cancer antigen-specific targeting by CTLs effectively regulates CSCs that drive cancer progression. In this study, we utilized data from public domains and performed various bioassays on human oral squamous cell carcinoma clinical samples and cell lines, including HSC-2 and HSC-3, to investigate the potential role of olfactory receptor family 7 subfamily C member 1 (OR7C1), a seven transmembrane G-protein-coupled olfactory receptor that is also expressed in nonolfactory tissues and was previously reported as a novel marker and target of colon cancer initiating cell-targeted immunotherapy, in CSC-targeted treatment against oral cancer. We found that the OR7C1 gene was expressed only in oral CSCs, and that CTLs reacted with human leukocyte antigen-A24-restricted OR7C1 oral CSC-specific peptides. Taken together, our findings suggest that OR7C1 represents a novel target for potent CSC-targeted immunotherapy in oral cancer.
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Carcinoma de Células Escamosas , Neoplasias Bucais , Receptores Odorantes , Humanos , Receptores Odorantes/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Imunoterapia , Linfócitos T Citotóxicos , Células-Tronco Neoplásicas/metabolismo , PeptídeosRESUMO
BACKGROUND: The coexistence of calcium pyrophosphate dihydrate crystal deposition (CPP) and synovial chondromatosis (SC) in the temporomandibular joint (TMJ) is rarely reported. CPP disease (CPPD) is complex arthritis synonymous with excessive pyrophosphate production and variable aberrations in mineral and organic phase metabolism of the joint cartilage, leading to local inundated CPP and crystal deposition of partially deciphered predispositions. Meanwhile, SC is a rare benign synovial joint proliferative disease of unclear etiology and has a low risk of malignant transformation. However, SC manifests severe joint disability and dysfunction because of connective tissue metaplasia of the synovial membrane, which forms cartilaginous nodules with or without calcifications or ossifications. These nodules often detach and form intra-articular loose bodies and very rarely within extraarticular spaces. CASE PRESENTATION: We report the case of a 61-year-old man to expand the body of literature on these unusual coexisting arthropathies of the TMJ. The patient presented to our hospital in 2020 with complaints of pain in the right TMJ and trismus for over 6 months. Radiographic assessments of the TMJ provided a preoperative provisional diagnosis of SC. However, the histopathology of the open biopsy revealed tumor-like lesions comprising several deposits of rhomboid and rod-shaped crystals that displayed positive birefringence in polarized light, confirming a coexistence of CPPD. A second-stage operation was performed for the complete removal of the loose bodies and chalk-like lesions including synovectomy. No evidence of recurrence was recorded after a follow-up of nearly 1.5 years. CONCLUSIONS: Isolated CPPD and SC of the TMJ are prevalent in the literature however, monoarticular coexistence of these diseases is rare, due to the lack of consistency in the diagnostic criteria in clinical practice. Moreover, optimal treatment depends on several considerations. This report delineated the molecular etiopathology and underscored the need for continued deciphering of the causal mechanisms of coexisting CPPD and SC of the TMJ. In addition, the importance of confirmatory testing for accurate diagnosis, and appropriate management of these diseases were discussed.
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Condrocalcinose , Condromatose Sinovial , Transtornos da Articulação Temporomandibular , Masculino , Humanos , Pessoa de Meia-Idade , Condromatose Sinovial/complicações , Condromatose Sinovial/diagnóstico por imagem , Condromatose Sinovial/cirurgia , Pirofosfato de Cálcio , Transtornos da Articulação Temporomandibular/complicações , Articulação Temporomandibular , Condrocalcinose/diagnóstico , Condrocalcinose/diagnóstico por imagemRESUMO
Hair loss, or alopecia, is associated with several psychosocial and medical comorbidities, and it remains an economic burden to individuals and the society. Alopecia is attributable to varied mechanisms and features a multifactorial predisposition, and the available conventional medical interventions have several limitations. Thus, several therapeutic strategies for alopecia in regenerative medicine are currently being explored, with increasing evidence suggesting that mesenchymal stem cell (MSC) implantation, MSC-derived secretome treatment, and blood-derived platelet-rich plasma therapies are potential treatment options. In this review, we searched the Cochrane Library, MEDLINE (PubMed), EMBASE, and Scopus using various combinations of terms, such as "stem cell," "alopecia," "hair loss," "Androgenetic alopecia," "male-pattern hair loss," "female-pattern hair loss," "regenerative hair growth," "cell therapy," "mesenchymal stem cells," "MSC-derived extracellular vesicles," "MSC-derived exosomes," and "platelet-rich plasma" and summarized the most promising regenerative treatments for alopecia. Moreover, further opportunities of improving efficacy and innovative strategies for promoting clinical application were discussed.
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Current trends indicate a growing interest among healthcare specialists and the public in the use of regenerative medicine-based approaches for skin regeneration. The approaches are categorised in either cell-based or cell-free therapies and are reportedly safe and effective. Cell-based therapies include mesenchymal stem cells (MSCs), tissue induced pluripotent stem cells (iPSCs), fibroblast-based products, and blood-derived therapies, such as those employing platelet-rich plasma (PRP) products. Cell-free therapies primarily involve the use of MSC-derived extracellular vesicles/exosomes. MSCs are isolated from various tissues, such as fat, bone marrow, umbilical cord, menstrual blood, and foetal skin, and expanded ex vivo before transplantation. In cell-free therapies, MSC exosomes, MSC-derived cultured media, and MSC-derived extracellular vesicles are collected from MSC-conditioned media or supernatant. In this review, a literature search of the Cochrane Library, MEDLINE (PubMed), EMBASE, and Scopus was conducted using several combinations of terms, such as 'stem', 'cell', 'aging', 'wrinkles', 'nasolabial folds', 'therapy', 'mesenchymal stem cells', and 'skin', to identify relevant articles providing a comprehensive update on the different regenerative medicine-based therapies and their application to skin regeneration. In addition, the regulatory perspectives on the clinical application of some of these therapies in Japan are highlighted.
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OBJECTIVE: Compared to other stem cells, the multipotency of human adipose-derived mesenchymal stem cells (ASCs) is limited. Effective approaches that trigger or enhance lineage-specific transdifferentiation are highly envisaged in the improvement of ASCs-based cell therapies. Using Immunofluorescence assays and the secretion of cardiac troponin T (cTnT) protein, we studied the impact of two substrates: Hydroxyapatite (HAp)-coated nonwoven polyethylene (PET)/polypropylene (PP) fabric and glass surfaces, representing 3 dimensional (D) and 2 D environments respectively, on the induction of cardiomyocytes - a non-mesodermal cell type from ASCs for 1-5 weeks. RESULTS: ASCs were successfully isolated from human adipose tissue under cGMP conditions. Within 1-3 weeks, expression of cTnT in the induced 3D cultures was overall significantly higher (P < 0.021) than that in the induced 2D cultures or controls (P < 0.0009). Remarkably, after 3 weeks of culture, cTnT secretion in the induced 3D cultures gradually declined, nearly reaching levels observed in the 2D cultures. The results show that HAp-coated nonwoven PE/PP fabric could enhance lineage-specific differentiation of ASCs toward cardiac-like cells. However, the fabric might suppress growth of the transformed cells. These preliminary findings encourage further interest in validating the fabric's potential in improving ASCs transdifferentiation.