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1.
Mol Genet Genomic Med ; 12(6): e2479, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38860502

ABSTRACT

BACKGROUND: As a screening method, inaccuracies in noninvasive prenatal screening (NIPS) exist, which are often attributable to biological factors. One such factor is the history of transplantation. However, there are still limited reports on such NIPS cases. METHODS: We report an NIPS case of a pregnant woman who had received a stem cell transplant from a male donor. To determine the karyotype in the woman's original cell, we performed chromosome microarray analysis (CMA) on her postnatal blood and oral mucosa. To comprehensively estimate the cell-free DNA (cfDNA) composition, we further performed standard NIPS procedures on the postnatal plasma. Moreover, we reviewed all published relevant NIPS case reports about pregnant women with transplantation history. RESULTS: NIPS showed a low-risk result for common trisomies with a fetal fraction of 65.80%. CMA on maternal white blood cells showed a nonmosaic male karyotype, while the oral mucosa showed a nonmosaic female karyotype. The proportion of donor's cfDNA in postnatal plasma was 94.73% based on the Y-chromosome reads ratio. The composition of cfDNA in maternal plasma was estimated as follows: prenatally, 13.60% maternal, 65.80% donor, and 20.60% fetal/placental, whereas postnatally, 5.27% maternal and 94.73% donor. CONCLUSIONS: This study expanded our understanding of the influence of stem cell transplantation on NIPS, allowing us to optimize NIPS management for these women.


Subject(s)
Cell-Free Nucleic Acids , Noninvasive Prenatal Testing , Humans , Female , Pregnancy , Male , Adult , Cell-Free Nucleic Acids/genetics , Cell-Free Nucleic Acids/blood , Noninvasive Prenatal Testing/methods , Stem Cell Transplantation , Tissue Donors , Trisomy/genetics
2.
Stem Cell Res Ther ; 15(1): 163, 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38853252

ABSTRACT

BACKGROUND: A rising population faces challenges with healing-impaired cutaneous wounds, often leading to physical disabilities. Adipose-derived stem cells (ASCs), specifically in the cell sheet format, have emerged as a promising remedy for impaired wound healing. Human platelet lysate (HPL) provides an attractive alternative to fetal bovine serum (FBS) for culturing clinical-grade ASCs. However, the potential of HPL sheets in promoting wound healing has not been fully investigated. This study aimed to explore the anti-fibrotic and pro-angiogenic capabilities of HPL-cultured ASC sheets and delve into the molecular mechanism. METHODS: A rat burn model was utilized to evaluate the efficacy of HPL-cultured ASC sheets in promoting wound healing. ASC sheets were fabricated with HPL, and those with FBS were included for comparison. Various analyses were conducted to assess the impact of HPL sheets on wound healing. Histological examination of wound tissues provided insights into aspects such as wound closure, collagen deposition, and overall tissue regeneration. Immunofluorescence was employed to assess the presence and distribution of transplanted ASCs after treatment. Further in vitro studies were conducted to decipher the specific factors in HPL sheets contributing to angiogenesis. RESULTS: HPL-cultured ASC sheets significantly accelerated wound closure, fostering ample and organized collagen deposition in the neo-dermis. Significantly more retained ASCs were observed in wound tissues treated with HPL sheets compared to the FBS counterparts. Moreover, HPL sheets mitigated macrophage recruitment and decreased subsequent wound tissue fibrosis in vivo. Immunohistochemistry also indicated enhanced angiogenesis in the HPL sheet group. The in vitro analyses showed upregulation of C-C motif chemokine ligand 5 (CCL5) and angiogenin in HPL sheets, including both gene expression and protein secretion. Culturing endothelial cells in the conditioned media compared to media supplemented with CCL5 or angiogenin suggested a correlation between CCL5 and the pro-angiogenic effect of HPL sheets. Additionally, through neutralizing antibody experiments, we further validated the crucial role of CCL5 in HPL sheet-mediated angiogenesis in vitro. CONCLUSIONS: The present study underscores CCL5 as an essential factor in the pro-angiogenic effect of HPL-cultured ASC sheets during the wound healing process. These findings highlight the potential of HPL-cultured ASC sheets as a promising therapeutic option for healing-impaired cutaneous wounds in clinical settings. Furthermore, the mechanism exploration yields valuable information for optimizing regenerative strategies with ASC products. BRIEF ACKNOWLEDGMENT: This research was supported by the National Science and Technology Council, Taiwan (NSTC112-2321-B-002-018), National Taiwan University Hospital (111C-007), and E-Da Hospital-National Taiwan University Hospital Joint Research Program (111-EDN0001, 112-EDN0002).


Subject(s)
Adipose Tissue , Blood Platelets , Chemokine CCL5 , Neovascularization, Physiologic , Wound Healing , Animals , Humans , Rats , Blood Platelets/metabolism , Chemokine CCL5/metabolism , Adipose Tissue/cytology , Adipose Tissue/metabolism , Stem Cells/metabolism , Stem Cells/cytology , Rats, Sprague-Dawley , Cells, Cultured , Male , Stem Cell Transplantation/methods , Angiogenesis
3.
Low Urin Tract Symptoms ; 16(4): e12527, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38867432

ABSTRACT

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic disease with limited treatment options. Current multidisciplinary approach targeting bladder inflammation and urothelial dysfunction has limited durable effect that major surgery is ultimately required for both Hunner and non-Hunner type IC. Various investigational attempts are underway to avoid such operations and preserve the urinary bladder. Stem cell therapy is a fascinating option for treating chronic illnesses. Stem cells can self-renew, restore damaged tissue, and have paracrine effects. The therapeutic efficacy and safety of stem cell therapy have been demonstrated in numerous preclinical models, primarily chemically induced cystitis rat models. Only one clinical trial (phase 1 study) has investigated the safety of human embryonic stem cell-derived mesenchymal stem cells in three Hunner-type IC patients. Under general anesthesia, participants underwent cystoscopic submucosal stem cell injection (2.0 × 107 stem cells/5 mL). No safety issues were reported up to 12 months of follow-up and long-term follow-up (up to 3 years). Although there were variations in therapeutic response, all patients reported significant improvement in pain at 1 month postoperatively. One patient underwent fulguration of the Hunner lesion after the trial, but others reported an overall improvement in pain. The analysis on phase 1/2a trial which had several modifications in protocol is currently ongoing. Despite several limitations that need to be overcome, stem cell therapy could be a potential therapeutic option for treating IC/BPS. Clinical outcome on phase 1/2a trial is important and might provide more insight into the clinical application of stem cell therapy for IC/BPS.


Subject(s)
Cystitis, Interstitial , Stem Cell Transplantation , Cystitis, Interstitial/therapy , Humans , Stem Cell Transplantation/methods , Animals , Mesenchymal Stem Cell Transplantation/methods
4.
PLoS One ; 19(6): e0302687, 2024.
Article in English | MEDLINE | ID: mdl-38848398

ABSTRACT

Xenogenesis has been recognized as a prospective method for producing channel catfish, Ictalurus punctatus ♀ × blue catfish, I. furcatus ♂ hybrids. The xenogenesis procedure can be achieved by transplanting undifferentiated stem cells derived from a donor fish into a sterile recipient. Xenogenesis for hybrid catfish embryo production has been accomplished using triploid channel catfish as a surrogate. However, having a surrogate species with a shorter maturation period, like white catfish (Ameiurus catus), would result in reduced feed costs, labor costs, and smaller body size requirements, making it a more suitable species for commercial applications where space is limited, and as a model species. Hence, the present study was conducted to assess the effectiveness of triploid white catfish as a surrogate species to transplant blue catfish stem cells (BSCs) and channel catfish stem cells (CSCs). Triploid white catfish fry were injected with either BSCs or CSCs labeled with PKH 26 fluorescence dye from 0 to 12 days post hatch (DPH). No significant differences in weight and length of fry were detected among BSCs and CSCs injection times (0 to 12 DPH) when fry were sampled at 45 and 90 DPH (P > 0.05). The highest survival was reported when fry were injected between 4.0 to 5.5 DPH (≥ 81.2%). At 45 and 90 DPH, cell and cluster area increased for recipients injected from 0 to 5.2 DPH, and the highest cluster area values were reported between 4.0 to 5.2 DPH. Thereafter, fluorescent cell and cluster area in the host declined with no further decrease after 10 DPH. At 45 DPH, the highest percentage of xenogens were detected when fry were injected with BSCs between 4.0 to 5.0 and CSCs between 3.0 to 5.0 DPH. At 90 DPH, the highest number of xenogens were detected from 4.0 to 6.0 DPH when injected with either BSCs or CSCs. The current study demonstrated the suitability of white catfish as a surrogate species when BSCs and CSCs were transplanted into triploid white catfish between 4.0 to 6.0 DPH (27.4 ± 0.4°C). Overall, these findings allow enhanced efficiency of commercializing xenogenic catfish carrying gametes of either blue catfish or channel catfish.


Subject(s)
Aquaculture , Catfishes , Triploidy , Animals , Aquaculture/methods , Stem Cells/cytology , Stem Cells/metabolism , Stem Cell Transplantation/methods , Ictaluridae/genetics , Female , Male
5.
Respir Res ; 25(1): 237, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849894

ABSTRACT

Pulmonary hypertension (PH) refers to a group of deadly lung diseases characterized by vascular lesions in the microvasculature and a progressive increase in pulmonary vascular resistance. The prevalence of PH has increased over time. Currently, the treatment options available for PH patients have limited efficacy, and none of them can fundamentally reverse pulmonary vascular remodeling. Stem cells represent an ideal seed with proven efficacy in clinical studies focusing on liver, cardiovascular, and nerve diseases. Since the potential therapeutic effect of mesenchymal stem cells (MSCs) on PH was first reported in 2006, many studies have demonstrated the efficacy of stem cells in PH animal models and suggested that stem cells can help slow the deterioration of lung tissue. Existing PH treatment studies basically focus on the paracrine action of stem cells, including protein regulation, exosome pathway, and cell signaling; however, the specific mechanisms have not yet been clarified. Apoptotic and afunctional pulmonary microvascular endothelial cells (PMVECs) and alveolar epithelial cells (AECs) are two fundamental promoters of PH although they have not been extensively studied by researchers. This review mainly focuses on the supportive communication and interaction between PMVECs and AECs as well as the potential restorative effect of stem cells on their injury. In the future, more studies are needed to prove these effects and explore more radical cures for PH.


Subject(s)
Hypertension, Pulmonary , Humans , Hypertension, Pulmonary/therapy , Hypertension, Pulmonary/metabolism , Animals , Stem Cell Transplantation/methods , Mesenchymal Stem Cell Transplantation/methods
6.
Recenti Prog Med ; 115(6): 286-289, 2024 Jun.
Article in Italian | MEDLINE | ID: mdl-38853731

ABSTRACT

Stem cell biology today represents the cornerstone of studies on cell therapies and regenerative medicine and is about to become the basis of clinical practice. It is not easy to predict the times and ways of science; however, the results achieved on multiple fronts demonstrate that this is a very promising area of research, as it could open important new horizons in the fight against human diseases.


Subject(s)
Regenerative Medicine , Stem Cell Transplantation , Stem Cells , Humans , Regenerative Medicine/methods , Stem Cell Transplantation/methods , Cell- and Tissue-Based Therapy/methods , Stem Cell Research
7.
Front Endocrinol (Lausanne) ; 15: 1397783, 2024.
Article in English | MEDLINE | ID: mdl-38846497

ABSTRACT

Objective: Various stem cell-loaded scaffolds have demonstrated promising endometrial regeneration and fertility restoration. This study aimed to evaluate the efficacy of stem cell-loaded scaffolds in treating uterine injury in animal models. Methods: The PubMed, Embase, Scopus, and Web of Science databases were systematically searched. Data were extracted and analyzed using Review Manager version 5.4. Improvements in endometrial thickness, endometrial glands, fibrotic area, and number of gestational sacs/implanted embryos were compared after transplantation in the stem cell-loaded scaffolds and scaffold-only group. The standardized mean difference (SMD) and confidence interval (CI) were calculated using forest plots. Results: Thirteen studies qualified for meta-analysis. Overall, compared to the scaffold groups, stem cell-loaded scaffolds significantly increased endometrial thickness (SMD = 1.99, 95% CI: 1.54 to 2.44, P < 0.00001; I² = 16%) and the number of endometrial glands (SMD = 1.93, 95% CI: 1.45 to 2.41, P < 0.00001; I² = 0). Moreover, stem cell-loaded scaffolds present a prominent effect on improving fibrosis area (SMD = -2.50, 95% CI: -3.07 to -1.93, P < 0.00001; I² = 36%) and fertility (SMD = 3.34, 95% CI: 1.58 to 5.09, P = 0.0002; I² = 83%). Significant heterogeneity among studies was observed, and further subgroup and sensitivity analyses identified the source of heterogeneity. Moreover, stem cell-loaded scaffolds exhibited lower inflammation levels and higher angiogenesis, and cell proliferation after transplantation. Conclusion: The evidence indicates that stem cell-loaded scaffolds were more effective in promoting endometrial repair and restoring fertility than the scaffold-only groups. The limitations of the small sample sizes should be considered when interpreting the results. Thus, larger animal studies and clinical trials are needed for further investigation. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024493132.


Subject(s)
Endometrium , Regeneration , Tissue Scaffolds , Female , Endometrium/physiology , Endometrium/cytology , Regeneration/physiology , Tissue Scaffolds/chemistry , Animals , Humans , Fertility/physiology , Stem Cells/cytology , Infertility, Female/therapy , Stem Cell Transplantation/methods
8.
Theranostics ; 14(8): 3358-3384, 2024.
Article in English | MEDLINE | ID: mdl-38855176

ABSTRACT

With the increase in the aging population, the occurrence of neurological disorders is rising. Recently, stem cell therapy has garnered attention due to its convenient sourcing, minimal invasiveness, and capacity for directed differentiation. However, there are some disadvantages, such as poor quality control, safety assessments, and ethical and logistical issues. Consequently, scientists have started to shift their attention from stem cells to extracellular vesicles due to their similar structures and properties. Beyond these parallels, extracellular vesicles can enhance biocompatibility, facilitate easy traversal of barriers, and minimize side effects. Furthermore, stem cell-derived extracellular vesicles can be engineered to load drugs and modify surfaces to enhance treatment outcomes. In this review, we summarize the functions of native stem cell-derived extracellular vesicles, subsequently review the strategies for the engineering of stem cell-derived extracellular vesicles and their applications in Alzheimer's disease, Parkinson's disease, and stroke, and discuss the challenges and solutions associated with the clinical translation of stem cell-derived extracellular vesicles.


Subject(s)
Alzheimer Disease , Extracellular Vesicles , Parkinson Disease , Stem Cells , Stroke , Humans , Extracellular Vesicles/transplantation , Extracellular Vesicles/metabolism , Parkinson Disease/therapy , Parkinson Disease/metabolism , Alzheimer Disease/therapy , Alzheimer Disease/metabolism , Animals , Stroke/therapy , Stem Cell Transplantation/methods
10.
Zhongguo Zhong Yao Za Zhi ; 49(9): 2316-2325, 2024 May.
Article in Chinese | MEDLINE | ID: mdl-38812132

ABSTRACT

This study aimed to investigate the intervention effect of tetramethylpyrazine(TMP) combined with transplantation of neural stem cells(NSCs) on middle cerebral artery occlusion(MCAO) rat model and to explore the mechanism of TMP combined with NSCs transplantation on ischemic stroke based on the regulation of stem cell biological behavior. MCAO rats were randomly divided into a model group, a TMP group, an NSCs transplantation group, and a TMP combined with NSCs transplantation group according to neurological function scores. A sham group was set up at the same time. The neurological function score was used to evaluate the improvement of neurological function in MCAO rats after TMP combined with NSCs transplantation. The proliferation, migration, and differentiation of NSCs were evaluated by BrdU, BrdU/DCX, BrdU/NeuN, and BrdU/GFAP immunofluorescence labeling. The protein expression of stromal cell-derived factor 1(SDF-1), C-X-C motif chemokine receptor 4(CXCR4), as well as oxidative stress pathway proteins nuclear factor erythroid 2-related factor 2(Nrf2), Kelch-like ECH-associated protein 1(KEAP1), heme oxygenase 1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1) was detected by Western blot to study the migration mechanism of TMP combined with NSCs. The results showed that TMP combined with NSCs transplantation significantly improved the neurological function score in MCAO rats. Immunofluorescence staining showed a significant increase in the number of BrdU~+, BrdU~+/DCX~+, BrdU~+/NeuN~+, and BrdU~+/GFAP~+ cells in the TMP, NSCs transplantation, and combined treatment groups, with the combined treatment group showing the most significant increase. Further Western blot analysis revealed significantly elevated expression of CXCR4 protein in the TMP, NSCs transplantation, and combined treatment groups, along with up-regulated protein expression of Nrf2, HO-1, and NQO1, and decreased KEAP1 protein expression. This study showed that both TMP and NSCs transplantation can promote the recovery of neurological function by promoting the proliferation, migration, and differentiation of NSCs, and the effect of TMP combined with NSCs transplantation is superior. The mechanism of action may be related to the activation of the Nrf2/HO-1/CXCR4 pathway.


Subject(s)
Brain Ischemia , Doublecortin Protein , NF-E2-Related Factor 2 , Neural Stem Cells , Pyrazines , Rats, Sprague-Dawley , Receptors, CXCR4 , Animals , Pyrazines/pharmacology , Neural Stem Cells/drug effects , Neural Stem Cells/transplantation , Neural Stem Cells/metabolism , Rats , Male , Receptors, CXCR4/metabolism , Receptors, CXCR4/genetics , Brain Ischemia/therapy , Brain Ischemia/metabolism , Brain Ischemia/drug therapy , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/genetics , Chemokine CXCL12/metabolism , Chemokine CXCL12/genetics , Kelch-Like ECH-Associated Protein 1/metabolism , Kelch-Like ECH-Associated Protein 1/genetics , Stem Cell Transplantation/methods , Cell Proliferation/drug effects , Cell Movement/drug effects , Humans , Reperfusion Injury/therapy , Reperfusion Injury/metabolism , Infarction, Middle Cerebral Artery/therapy , NAD(P)H Dehydrogenase (Quinone)/metabolism , NAD(P)H Dehydrogenase (Quinone)/genetics
11.
Sci Rep ; 14(1): 12545, 2024 05 31.
Article in English | MEDLINE | ID: mdl-38822024

ABSTRACT

Multiple sclerosis (MS) is a common autoimmune neurological disease affecting patients' motor, sensory, and visual performance. Stem Cell Transplantation (SCT) is a medical intervention where a patient is infused with healthy stem cells with the purpose of resetting their immune system. SCT shows remyelinating and immunomodulatory functions in MS patients, representing a potential therapeutic option. We conducted this systematic review and meta-analysis that included randomized control trials (RCTs) of SCT in MS patients to investigate its clinical efficacy and safety, excluding observational and non-English studies. After systematically searching PubMed, Web of Science, Scopus, and Cochrane Library until January 7, 2024, nine RCTs, including 422 patients, were eligible. We assessed the risk of bias (ROB) in these RCTs using Cochrane ROB Tool 1. Data were synthesized using Review Manager version 5.4 and OpenMeta Analyst software. We also conducted subgroup and sensitivity analyses. SCT significantly improved patients expanded disability status scale after 2 months (N = 39, MD = - 0.57, 95% CI [- 1.08, - 0.06], p = 0.03). SCT also reduced brain lesion volume (N = 136, MD = - 7.05, 95% CI [- 10.69, - 3.4], p = 0.0002). The effect on EDSS at 6 and 12 months, timed 25-foot walk (T25-FW), and brain lesions number was nonsignificant. Significant adverse events (AEs) included local reactions at MSCs infusion site (N = 25, RR = 2.55, 95% CI [1.08, 6.03], p = 0.034) and hematological disorders in patients received immunosuppression and autologous hematopoietic SCT (AHSCT) (N = 16, RR = 2.33, 95% CI [1.23, 4.39], p = 0.009). SCT can improve the disability of MS patients and reduce their brain lesion volume. The transplantation was generally safe and tolerated, with no mortality or significant serious AEs, except for infusion site reactions after mesenchymal SCT and hematological AEs after AHSCT. However, generalizing our results is limited by the sparse number of RCTs conducted on AHSCT. Our protocol was registered on PROSPERO with a registration number: CRD42022324141.


Subject(s)
Multiple Sclerosis , Randomized Controlled Trials as Topic , Stem Cell Transplantation , Humans , Multiple Sclerosis/therapy , Stem Cell Transplantation/methods , Stem Cell Transplantation/adverse effects , Treatment Outcome
12.
Biofabrication ; 16(3)2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38810632

ABSTRACT

Systemic stem cell therapies hold promise for treating severe diseases, but their efficiency is hampered by limited migration of injected stem cells across vascular endothelium towards diseased tissues. Understanding transendothelial migration is crucial for improving therapy outcomes. We propose a novel 3Din vitrovessel model that aids to unravel these mechanisms and thereby facilitates stem cell therapy development. Our model simulates inflammation through cytokine diffusion from the tissue site into the vessel. It consists of a biofabricated vessel embedded in a fibrin hydrogel, mimicking arterial wall composition with smooth muscle cells and fibroblasts. The perfusable channel is lined with a functional endothelium which expresses vascular endothelial cadherin, provides an active barrier function, aligns with flow direction and is reconstructed byin situtwo-photon-microscopy. Inflammatory cytokine release (tumor necrosis factorα, stromal-derived factor (1) is demonstrated in both a transwell assay and the 3D model. In proof-of-principle experiments, mesoangioblasts, known as a promising candidate for a stem cell therapy against muscular dystrophies, are injected into the vessel model, showing shear-resistant endothelial adhesion under capillary-like flow conditions. Our 3Din vitromodel offers significant potential to study transendothelial migration mechanisms of stem cells, facilitating the development of improved stem cell therapies.


Subject(s)
Transendothelial and Transepithelial Migration , Humans , Stem Cell Transplantation , Models, Biological , Stem Cells/cytology , Stem Cells/metabolism , Hydrogels/chemistry , Tissue Engineering , Cell Movement
13.
Stem Cell Res Ther ; 15(1): 136, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38715083

ABSTRACT

BACKGROUND: Alzheimer's disease (AD) is a prevalent form of dementia leading to memory loss, reduced cognitive and linguistic abilities, and decreased self-care. Current AD treatments aim to relieve symptoms and slow disease progression, but a cure is elusive due to limited understanding of the underlying disease mechanisms. MAIN CONTENT: Stem cell technology has the potential to revolutionize AD research. With the ability to self-renew and differentiate into various cell types, stem cells are valuable tools for disease modeling, drug screening, and cell therapy. Recent advances have broadened our understanding beyond the deposition of amyloidß (Aß) or tau proteins in AD to encompass risk genes, immune system disorders, and neuron-glia mis-communication, relying heavily on stem cell-derived disease models. These stem cell-based models (e.g., organoids and microfluidic chips) simulate in vivo pathological processes with extraordinary spatial and temporal resolution. Stem cell technologies have the potential to alleviate AD pathology through various pathways, including immunomodulation, replacement of damaged neurons, and neurotrophic support. In recent years, transplantation of glial cells like oligodendrocytes and the infusion of exosomes have become hot research topics. CONCLUSION: Although stem cell-based models and therapies for AD face several challenges, such as extended culture time and low differentiation efficiency, they still show considerable potential for AD treatment and are likely to become preferred tools for AD research.


Subject(s)
Alzheimer Disease , Stem Cell Transplantation , Alzheimer Disease/therapy , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Humans , Stem Cell Transplantation/methods , Animals , Stem Cells/metabolism , Stem Cells/cytology
14.
Stem Cell Res Ther ; 15(1): 153, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38816870

ABSTRACT

BACKGROUND: The therapeutic status of allogeneic stem cell transplantation (allo-SCT) as a post-remission treatment for patients with high-risk acute myeloid leukemia (AML) was well-accepted. However, the optimal treatment for patients with low/favorable- or intermediate-risk AML who achieve complete remission has remained controversial. Therefore, we conducted a network meta-analysis to discuss this disputed problem. METHODS: We compared the effects of treatment strategies including allo-SCT, autologous stem cell transplantation (auto-SCT) and consolidation chemotherapy (CT) for patients with low/favorable- or intermediate-risk AML. The pooled HRs and 95% CIs for overall survival and disease-free survival were estimated with Stata12 and R software. Thirty clinical studies with 6682 patients were included in the meta-analysis. RESULTS: The results indicated that the treatment outcome of allo-SCT was the best, followed by auto-SCT, and CT was likely the worst in the total AML patients. In patients with low/favorable-risk AML, the treatment outcome of auto-SCT was likely ranked first, followed by allo-SCT, and CT was the worst. In patients with intermediate-risk AML, the treatment outcome of haploidentical stem cell transplantation (haplo-SCT) was the best, followed by allo-SCT (excluding haplo-SCT), and auto-SCT and CT were the worst. However, the median age of the haplo-SCT group was much younger than that of the control group, which may be one of the reasons for the better prognosis of the haplo-SCT group. CONCLUSIONS: Patients with low/favorable- and intermediate-risk (non-high-risk) AML should prioritize allo-SCT if they are eligible for transplantation, and auto-SCT is optional. However, in the subgroup analysis, auto-SCT was the optimal treatment choice for patients with low/favorable-risk AML, and allo-SCT was the priority selection for patients with intermediate-risk AML, especially young patients. These findings could provide references for clinical practice.


Subject(s)
Leukemia, Myeloid, Acute , Humans , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/mortality , Hematopoietic Stem Cell Transplantation/methods , Transplantation, Homologous , Transplantation, Autologous , Stem Cell Transplantation , Disease-Free Survival , Network Meta-Analysis , Treatment Outcome , Male
15.
Transfusion ; 64(6): 1059-1067, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38693056

ABSTRACT

BACKGROUND: Abdominal adhesions are the most common surgical complication and without reliable prophylactics. This study presents a novel rat model for abdominal adhesions and reports pilot results of human placental stem cell (hPSC)-based therapies. METHODS: Forty-four (n = 44) male Sprague-Dawley rats (250-350 g) were used in the experiment. Of these, thirty-eight (n = 38) were included in a preliminary data set to determine a minimum treatment effect. Adhesions were created in a reproducible model to the abdominal wall and between organs. Experimental groups included the control group (Model No Treatment, MNT), Plasmalyte A (Media Alone, MA, 10 mL), hPSC (5 × 106 cells/10 mL Plasmalyte A), hPSC-CM (hPSC secretome, conditioned media) in 10 mL Plasmalyte A, Seprafilm™ (Baxter, Deerfield, IL), and sham animals (laparotomy only). Treatments were inserted intraperitoneally (IP) and the study period was 14 days post-operation. Results are reported as the difference between means of an index statistic (AIS, Animal Index Score) and compared by ANOVA with pairwise comparison. RESULTS: The overall mean AIS was 23 (SD 6.16) for the MNT group with an average of 75% of ischemic buttons involved in abdominal adhesions. Treatment groups MA (mean overall AIS 17.33 SD 6.4), hPSC (mean overall AIS 13.86 SD 5.01), hPSC-CM (mean overall AIS 13.13 SD 6.15), and Seprafilm (mean overall AIS 13.43 SD 9.11) generated effect sizes of 5.67, 9.14, 9.87, and 9.57 decrease in mean overall AIS, respectively, versus the MNT. DISCUSSION: The presented rat model and scoring system represent the clinical adhesion disease process. hPSC-based interventions significantly reduce abdominal adhesions in this pilot dataset.


Subject(s)
Rats, Sprague-Dawley , Tissue Adhesions/prevention & control , Animals , Humans , Rats , Female , Pilot Projects , Male , Pregnancy , Postoperative Complications/prevention & control , Postoperative Complications/etiology , Disease Models, Animal , Placenta/cytology , Stem Cell Transplantation/methods , Stem Cells/cytology
16.
PeerJ ; 12: e17299, 2024.
Article in English | MEDLINE | ID: mdl-38799055

ABSTRACT

Background: Ageing is a key risk factor for cardiovascular disease and is linked to several alterations in cardiac structure and function, including left ventricular hypertrophy and increased cardiomyocyte volume, as well as a decline in the number of cardiomyocytes and ventricular dysfunction, emphasizing the pathological impacts of cardiomyocyte ageing. Dental pulp stem cells (DPSCs) are promising as a cellular therapeutic source due to their minimally invasive surgical approach and remarkable proliferative ability. Aim: This study is the first to investigate the outcomes of the systemic transplantation of DPSCs in a D-galactose (D-gal)-induced rat model of cardiac ageing. Methods. Thirty 9-week-old Sprague-Dawley male rats were randomly assigned into three groups: control, ageing (D-gal), and transplanted groups (D-gal + DPSCs). D-gal (300 mg/kg/day) was administered intraperitoneally daily for 8 weeks. The rats in the transplantation group were intravenously injected with DPSCs at a dose of 1 × 106 once every 2 weeks. Results: The transplanted cells migrated to the heart, differentiated into cardiomyocytes, improved cardiac function, upregulated Sirt1 expression, exerted antioxidative effects, modulated connexin-43 expression, attenuated cardiac histopathological alterations, and had anti-senescent and anti-apoptotic effects. Conclusion: Our results reveal the beneficial effects of DPSC transplantation in a cardiac ageing rat model, suggesting their potential as a viable cell therapy for ageing hearts.


Subject(s)
Dental Pulp , Galactose , Myocytes, Cardiac , Rats, Sprague-Dawley , Animals , Male , Rats , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/transplantation , Myocytes, Cardiac/drug effects , Dental Pulp/cytology , Stem Cell Transplantation/methods , Aging/physiology , Sirtuin 1/metabolism , Cell Differentiation/drug effects , Connexin 43/metabolism , Disease Models, Animal , Stem Cells/metabolism , Stem Cells/cytology , Apoptosis/drug effects
17.
Blood Cancer J ; 14(1): 86, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38806475

ABSTRACT

Multiple myeloma (MM) therapeutics have evolved tremendously in recent years, with significant improvement in patient outcomes. As newer treatment options are developed, stem cell transplant (SCT) remains an important modality that provides excellent disease control and delays the progression of disease. Over the years, SCT use has increased overall in the U.S., but two distinct gaps remain, including suboptimal use overall and racial-ethnic disparities. We evaluated the National Cancer Database (NCDB) to study what sociodemographic factors might play a role within a given racial-ethnic group leading to disparate SCT utilization, such that targeted approaches can be developed to optimize SCT use for all. In nearly 112,000 cases belonging to mutually exclusive categories of non-Hispanic Whites (NHW), non-Hispanic Blacks (NHB), Hispanics, non-Hispanic Asians (NHA), and others, we found certain factors including age, comorbidity index, payor type, facility type (academic vs. community) and facility volume to be uniformly associated with SCT use for all the racial-ethnic groups, while gender was not significant for any of the groups. There were several other factors that had a differential impact on SCT utilization among the various race-ethnicity groups studied, including year of diagnosis (significant for NHW, NHB, and Hispanics), income level (significant for NHW and Hispanics), literacy level (significant for NHW and NHB), and geographic location of the treatment facility (significant for NHW and NHA). The suboptimal SCT utilization overall in the U.S. suggests that there may be room for improvement for all, even including the majority NHW, while we continue to work on factors that lead to disparities for the traditionally underserved populations. This study helps identify sociodemographic factors that may play a role specifically in each group and paves the way to devise targeted solutions such that resource utilization and impact can be maximized.


Subject(s)
Healthcare Disparities , Multiple Myeloma , Humans , Multiple Myeloma/therapy , Multiple Myeloma/epidemiology , Male , Female , Middle Aged , Aged , United States/epidemiology , Adult , Stem Cell Transplantation , Hematopoietic Stem Cell Transplantation
18.
Int J Biol Macromol ; 268(Pt 2): 131874, 2024 May.
Article in English | MEDLINE | ID: mdl-38692547

ABSTRACT

Serious orthopedic disorders resulting from myriad diseases and impairments continue to pose a considerable challenge to contemporary clinical care. Owing to its limited regenerative capacity, achieving complete bone tissue regeneration and complete functional restoration has proven challenging with existing treatments. By virtue of cellular regenerative and paracrine pathways, stem cells are extensively utilized in the restoration and regeneration of bone tissue; however, low survival and retention after transplantation severely limit their therapeutic effect. Meanwhile, biomolecule materials provide a delivery platform that improves stem cell survival, increases retention, and enhances therapeutic efficacy. In this review, we present the basic concepts of stem cells and extracellular vesicles from different sources, emphasizing the importance of using appropriate expansion methods and modification strategies. We then review different types of biomolecule materials, focusing on their design strategies. Moreover, we summarize several forms of biomaterial preparation and application strategies as well as current research on biomacromolecule materials loaded with stem cells and extracellular vesicles. Finally, we present the challenges currently impeding their clinical application for the treatment of orthopedic diseases. The article aims to provide researchers with new insights for subsequent investigations.


Subject(s)
Extracellular Vesicles , Stem Cells , Extracellular Vesicles/chemistry , Humans , Stem Cells/cytology , Animals , Biocompatible Materials/chemistry , Bone Diseases/therapy , Bone Regeneration , Stem Cell Transplantation/methods , Macromolecular Substances/chemistry , Macromolecular Substances/pharmacology
19.
J Law Med ; 31(1): 105-121, 2024 May.
Article in English | MEDLINE | ID: mdl-38761392

ABSTRACT

Stem cell therapies have emerged as a miracle cure that could treat diseases and conditions. The past decade has seen the rapid growth of private clinics in some nations, including Australia, offering stem cell treatments largely untested and unsupported by clinical trials. These putative treatments have caused adverse events, some of which were serious and even fatal. The unscrupulous businesses exploit vulnerable and desperate patients who falsely believe these unproven therapies are their only salvation to cure different illnesses and conditions. This article emphasises the importance of strict oversight to ensure that only safe stem cell products reach patients, given the largely vulnerable patient base and the magnitude of risks involved. It examines the effectiveness of Australia's regulatory environment governing stem cell therapies to restrict the advertisement of dangerous and unproven stem cell therapies and the enforceability of these measures.


Subject(s)
Stem Cell Transplantation , Humans , Australia , Stem Cell Transplantation/legislation & jurisprudence , Government Regulation
20.
Neurochem Res ; 49(6): 1450-1467, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38720090

ABSTRACT

Wernicke's encephalopathy (WE) is a major central nervous system disorder resulting from thiamine deficiency (TD) in which a number of brain regions can develop serious damage including the thalamus and inferior colliculus. Despite decades of research into the pathophysiology of TD and potential therapeutic interventions, little progress has been made regarding effective treatment following the development of brain lesions and its associated cognitive issues. Recent developments in our understanding of stem cells suggest they are capable of repairing damage and improving function in different maladys. This article puts forward the case for the potential use of stem cell treatment as a therapeutic strategy in WE by first examining the effects of TD on brain functional integrity and its consequences. The second half of the paper will address the future benefits of treating TD with these cells by focusing on their nature and their potential to effectively treat neurodegenerative diseases that share some overlapping pathophysiological features with TD. At the same time, some of the obstacles these cells will have to overcome in order to become a viable therapeutic strategy for treating this potentially life-threatening illness in humans will be highlighted.


Subject(s)
Stem Cell Transplantation , Thiamine Deficiency , Wernicke Encephalopathy , Humans , Thiamine Deficiency/therapy , Thiamine Deficiency/complications , Animals , Wernicke Encephalopathy/etiology , Wernicke Encephalopathy/therapy , Stem Cell Transplantation/methods , Brain/pathology , Brain/metabolism
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