(1) Background: The aim of the current pilot study was to describe the long-term effects of a single intra-articular injection of autologous stromal vascular fraction (SVF) with platelet-rich plasma (PRP) in dogs with confirmed elbow OA, using orthopedic lameness scoring and kinetic and kinematic gait analysis. For comparison of normal long-term variation of gait over time, a group of healthy control dogs (CDs) was also evaluated. (2) Methods: A prospective longitudinal clinical pilot study investigating 19 client-owned dogs with elbow OA (OADs) treated with SVF and PRP and eight CDs not receiving treatment. The OAD and CD groups were evaluated before and after 6 and at least 12 months following treatment with SVF and PRP (OAD group) and twice with a six-month interval (CD group), respectively, through orthopedic examinations, goniometry, and kinetic and kinematic analyses (seven variables). (3) Results: The OAD had an increase in fore-hind peak force symmetry ≥12 months after treatment (p < 0.05), but no other objective variables changed over time. Orthopedic consensus scores had improved at ≥six months follow-up evaluation (p < 0.05). None of the investigated gait variables had changed at ≥six months follow-up evaluation in the CD group. (4) Conclusions: The current study could not confirm a significant benefit from SVF and PRP treatment in OADs, but future studies should be conducted in order to fully evaluate the potential of the treatment. The improvement seen in fore-hindlimb symmetry may represent an improvement in gait or an incidental finding.

UNASSIGNED: High-dose chemotherapy followed by autologous hematopoietic stem cell support is recommended in the treatment of eligible multiple myeloma (MM) patients. The aim of this study was to compare the efficacy and safety of steady-state versus chemotherapy-based stem cell mobilization in our Hungarian patient population.
UNASSIGNED: The subjects were 210 MM patients who underwent stem cell mobilization procedure between 2018 and 2022. Solo granulocyte colony-stimulating factor (G-CSF) was administered in 104 cases, while 106 patients received chemotherapy which was followed by G-CSF administration. We evaluated the ratio of successful mobilizations, the amount of collected stem cells, the incidence of infections and cost-effectivity in the two groups.
UNASSIGNED: In the steady-state group, there was a significantly higher need for plerixafor (45% vs. 13%, P < 0.001), unsuccessful stem cell mobilization was more frequent (11% vs. 3%, P = 0.024) and the mean amount of collected stem cells was lower (6.9 vs. 9.8 × 106, P < 0.001) than in the chemotherapy group. However, infections were less frequent (4% vs. 27%, P < 0.001) and the number of days spent in hospital was significantly lower (6 vs. 14 days, P < 0.001). Plerixafor was more frequently administered in those who had received lenalidomide or daratumumab than in those who had been treated with other regimens (41% vs. 23%, P = 0.007 and 78% vs. 23%, P < 0.001, respectively).
UNASSIGNED: Steady-state mobilization is a safe method; however, the higher rate of plerixafor administration and unsuccessful attempts may question its superiority to chemomobilization.

UNASSIGNED: Stem cell transplantation is a clinical approach used to treat certain types of cancers, such as hematologic malignancies. Graft-versus-host disease (GVHD) occurs in 30-70% of cases and often diminishes the quality of life of transplant patients. This study aimed to determine the prevalence of vaginal complications of GVHD following hematopoietic stem cell transplantation.
UNASSIGNED: This study employed an analytical cross-sectional design. All patients referred to Shariati Hospital in Tehran between 2019 and 2020 who underwent hematopoietic stem cell transplantation were considered for inclusion in this study if they met the inclusion criteria. Inclusion criteria encompassed nonnot sexually active women aged 18-70 who received stem cell transplantation more than 100 days prior. Exclusion criteria comprised patients who experienced GVHD during the first 100 days posttransplantation. Additionally, individuals over 75 and patients with metastatic cancer were excluded.
UNASSIGNED: A total of 55 patients were recruited, with ages averaging 40±9.9 years for recipients and 38.5±12.8 years for donors. Notably, 63.3 and 58.2% of patients exhibited oral and ocular symptoms, respectively. Regarding genital involvement, 49.1% experienced vaginal symptoms, while 25.5% had vulvar involvement. Among the 27 patients with vaginal involvement, two (7.4%) were categorized as mild, 17 (63%) as moderate, and eight (29.6%) as severe. Univariate analysis identified reduced vaginal discharge [odds ratio (OR=6.56)], vaginal tightness (OR=6.23), pelvic pain (OR=5.50), and vaginal involvement (OR=3.81) as significant predictors of other organ symptoms. Moreover, vaginal involvement (OR=3.68) emerged as the sole significant predictor of the cooccurrence of oral, ocular, and other organ symptoms. In the multivariate analysis, reduced vaginal discharge (OR=8.24) and vaginal tightness (OR=3.92) significantly predicted other organ symptoms (P=0.009).
UNASSIGNED: Reduced vaginal discharge and vaginal tightness remained significant predictors of other organ symptoms.

Natural products have attracted great interest in the development of tissue engineering. Recent studies have demonstrated that unsaturated fatty acids found in natural plant seed oil may exhibit positive osteogenic effects; however, few in vivo studies have focused on the use of plant seed oil for bone regeneration. The aim of this study is to investigate the effects of seed oil found in Sapindus mukorossi (S. mukorossi) on the osteogenic differentiation of mesenchymal stem cells and bone growth in artificial bone defects in vivo. In this study, Wharton-jelly-derived mesenchymal stem cells (WJMSCs) were co-cultured with S. mukorossi seed oil. Cellular osteogenic capacity was assessed using Alizarin Red S staining. Real-time PCR was carried out to evaluate ALP and OCN gene expression. The potential of S. mukorossi seed oil to enhance bone growth was assessed using an animal model. Four 6 mm circular defects were prepared at the parietal bone of New Zealand white rabbits. The defects were filled with hydrogel and hydrogel-S. mukorossi seed oil, respectively. Quantitative analysis of micro-computed tomography (Micro-CT) and histological images was conducted to compare differences in osteogenesis between oil-treated and untreated samples. Although our results showed no significant differences in viability between WJMSCs treated with and without S. mukorossi seed oil, under osteogenic conditions, S. mukorossi seed oil facilitated an increase in mineralized nodule secretion and upregulated the expression of ALP and OCN genes in the cells (p < 0.05). In the animal study, both micro-CT and histological evaluations revealed that new bone formation in artificial bone defects treated with S. mukorossi seed oil were nearly doubled compared to control defects (p < 0.05) after 4 weeks of healing. Based on these findings, it is reasonable to suggest that S. mukorossi seed oil holds promise as a potential candidate for enhancing bone healing efficiency in bone tissue engineering.

BACKGROUND: Mesenchymal stromal/stem cells (MSCs) play a critical role in wound healing. Corlicyte® is an MSC product derived from allogeneic umbilical cord tissue donated under an institutional review board-approved protocol and processed in accordance with section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act. This open-label phase 1 trial was performed under a United States Food and Drug Administration Investigational New Drug Application to establish the safety and tolerability of Corlicyte® in patients with diabetes and chronic diabetic foot ulcer (DFU).
METHODS: Escalating doses were applied topically twice a week for up to 8 weeks after ulcer debridement, wound photography, and measurement. Subjects were followed for 4 weeks after the treatment phase. Adverse events were assessed at every visit.
RESULTS: Nine subjects in 2 dosing cohorts completed the trial. No subjects experienced a serious adverse reaction to Corlicyte® or the development of anti-human leukocyte antigen (HLA) antibodies. Sixty percentage of subjects in the lower dose cohort experienced ulcer closure by Day 70 of follow-up, while the mean ulcer size was reduced by 54-67% in the other subjects.
CONCLUSIONS: Topical administration of Corlicyte®, a novel biologic therapy consisting of allogeneic umbilical cord lining MSCs, appeared safe and tolerable and resulted in a significant decrease in ulcer area, demonstrating its potential as a therapy for healing of chronic DFU.

The purest and unrestricted source of stem cells is the enamel of the teeth. Dental stem cells (DSCs), which are simple to get, quick to use, and reasonably priced, have the potential to be used in a variety of promising therapeutic applications. Due to their capacity for self-renewal, they are employed to treat significant flaws brought about by diseases, injuries, or surgical procedures. However, they are constrained by moral and ethical issues, as well as challenges with isolation, culturing, and implantation. DSCs are used in the rebuilding of orofacial structures because they retain the ability to differentiate into neurogenic, adipogenic, and odontogenic components. Before stem cell implantation, scaffolding that has been treated with growth hormones and bone morphogenic proteins is crucial. A self-administered questionnaire was used for a cross-sectional study (n = 200) that collected data on demographics, knowledge of stem cells, and attitude statements. Statistical Package for Social Software version 20.0 was used to analyze the data. This study seeks to learn more about professional groups\' perceptions of stem cell research in Tamil Nadu and their knowledge and awareness of DSCs.

Histone modifications are associated with regulation of gene expression that controls a vast array of biological processes. Often, these associations are drawn by correlating the genomic location of a particular histone modification with gene expression or phenotype; however, establishing a causal relationship between histone marks and biological processes remains challenging. Consequently, there is a strong need for experimental approaches to directly manipulate histone modifications. A class of mutations on the N-terminal tail of histone H3, lysine-to-methionine (K-to-M) mutations, was identified as dominant-negative inhibitors of histone methylation at their respective and specific residues. The dominant-negative nature of K-to-M mutants makes them a valuable tool for studying the function of specific methylation marks on histone H3. Here, we review recent applications of K-to-M mutations to understand the role of histone methylation during development and homeostasis. We highlight important advantages and limitations that require consideration when using K-to-M mutants, particularly in a developmental context.

BACKGROUND: Perianal fistulas (PF) affect one-third patients with Crohn\'s disease (CD) with limited therapeutic options. There is dearth of literature on safety and efficacy of bone marrow-derived mesenchymal stromal cells (BMSCs) in this population.
METHODS: An open-label, phase I/II, single-arm study was conducted involving local administration of human allogeneic bone marrow-derived mesenchymal stromal cells in perianal fistula of patients with Crohn\'s disease refractory to standard therapies. Clinical severity and biomarkers were assessed at baseline and periodically until week 104 , and MRI at week 24 and 104. Primary and secondary objectives were to assess safety and efficacy respectively. Fistula remission was complete closure of fistula openings with < 2 cm perianal collection on MRI, and fistula response was decrease in drainage by ≥ 50%. Change in perianal disease activity index, quality-of-life and Van Assche index on MRI over time was assessed using mixed-effect linear regression model.
RESULTS: Ten patients (male:8, mean age:27.4 ± 12.0years) were recruited. Self-resolving procedure-related adverse events occurred in three patients, with no follow-up adverse events. In intention to treat analysis at week 24, two patients (20%) achieved fistula remission and seven (70%) had fistula response. At week 52, two (20%) patients were in remission and seven (70%) maintained response. At 104 weeks, two (20%) patients maintained response and one (10%) was in remission. Statistically significant decrease in perianal disease activity index (P = 0.008), Van Assche Index (P = 0.008) and improvement in quality-of-life (P = 0.001) were observed over time.
CONCLUSIONS: Allogeneic BMSCs are safe and effective for the treatment of perianal fistulizing CD with significant improvement in clinical severity and radiological healing.
BACKGROUND: The study was prospectively registered on Clinical trials registry - India (CTRI), CTRI/2020/01/022743 on 14 January 2020, http://ctri.nic.in .

BACKGROUND: Skeletal morbidity in patients with cancer has a major impact on the quality of life, and preserving bone health while improving outcomes is an important goal of modern antitumor treatment strategies. Despite their widespread use in early disease stages, the effects of immune checkpoint inhibitors (ICIs) on the skeleton are still poorly defined. Here, we initiated a comprehensive investigation of the impact of ICIs on bone health by longitudinal assessment of bone turnover markers in patients with cancer and by validation in a novel bioengineered 3D model of bone remodeling.
METHODS: An exploratory longitudinal study was conducted to assess serum markers of bone resorption (C-terminal telopeptide, CTX) and formation (procollagen type I N-terminal propeptide, PINP, and osteocalcin, OCN) before each ICI application (programmed cell death 1 (PD1) inhibitor or programmed death-ligand 1 (PD-L1) inhibitor) for 6 months or until disease progression in patients with advanced cancer and no evidence of bone metastases. To validate the in vivo results, we evaluated osteoclast (OC) and osteoblast (OB) differentiation on treatment with ICIs. In addition, their effect on bone remodeling was assessed by immunohistochemistry, confocal microscopy, and proteomics analysis in a dynamic 3D bone model.
RESULTS: During the first month of treatment, CTX levels decreased sharply but transiently. In contrast, we observed a delayed increase of serum levels of PINP and OCN after 4 months of therapy. In vitro, ICIs impaired the maturation of preosteoclasts by inhibiting STAT3/NFATc1 signaling but not JNK, ERK, and AKT while lacking any direct effect on osteogenesis. However, using our bioengineered 3D bone model, which enables the simultaneous differentiation of OB and OC precursor cells, we confirmed the uncoupling of the OC/OB activity on exposure to ICIs by demonstrating impaired OC maturation along with increased OB differentiation.
CONCLUSIONS: Our study indicates that the inhibition of the PD1/PD-L1 signaling axis interferes with bone turnover and may exert a protective effect on bone by indirectly promoting osteogenesis.

This study aimed to compare the clinically established autologous extrasynovial tendon graft to a newly developed tissue-engineered allograft (Eng-allograft) in terms of functional outcomes following flexor tendon reconstruction in a canine model. The second and fifth flexor digitorum profundus (FDP) tendons from 16 dogs were transected and repaired in Zone II. After 6 weeks of cage activity, the repaired tendons were intentionally ruptured, creating a clinically relevant model for reconstruction. The re-ruptured FDP tendons were then reconstructed using either the clinically standard autologous extrasynovial tendon graft or the Eng-allograft, which had been revitalized with autologous bone marrow-derived mesenchymal stem cells (BMSCs) and synovialized using carbodiimide derivatized synovial fluid (cd-SYN). Following 12 weeks of postoperative rehabilitation, the functional outcomes of the surgical digits were evaluated. The Eng-allograft group exhibited improved digital function, including lower digit work of flexion and reduced adhesion status, while maintaining similar tendon gliding resistance compared to the autograft group. However, the failure load of both the distal and proximal host/graft conjunctions in the Eng-allograft group was significantly lower than that of the autograft group with higher graft rupture at the host-graft junction. In conclusion, the decellularized allogenic intrasynovial tendon, when revitalized BMSCs and synovialized with cd-SYN, demonstrates positive effects on digital function improvement and adhesion reduction. However, the healing at both proximal and distal graft/host junctions is far lower than the autograft. Further research is needed to enhance the healing capacity of allograft conjunctions, aiming to achieve a comparable level of healing seen with autografts.