Injection Of Stem Cells Research Articles

MODL-01. TRACTABLE PATIENT-DERIVED MODELS FOR PRECLINICAL THERAPEUTIC STUDIES OF CNS METASTASES

Abstract INTRODUCTION Brain metastases are the most common brain tumors and occur in 10-30% of cancer patients, whereas leptomeningeal disease (LMD) occurs in approximately 5% of adults with systemic malignancies. Tractable preclinical disease models that faithfully represent metastasis to the brain and recapitulate LMD are needed to improve our understanding of the biological basis of CNS disease as well developing effective therapeutic strategies. Our goal in this study was to generate representative preclinical disease models using two methods. METHODS We isolated tumor cells from CSF of 16 patients with cytologically proven LMD (9 NSCLC, 1 melanoma, 1 ovarian cancer, 1 endometrial cancer, and 4 breast cancer) and implanted the cells subcutaneously into the flank of immunocompromised mice. Cell lines were also generated from PDX tissues. Models were characterized by next-generation sequencing (NGS). We also generated a model of CNS metastasis of kinase-driven sarcoma by intracardiac (IC) injection of human mesenchymal stem cells (HMSC) expressing a SPECC1L::RET fusion (CRISPR-Cas9 gene editing). The cells (HMSC-RET) were also labeled with a luciferase construct to allow non-invasive bioluminescence imaging. RESULTS We established three PDX models (2 lung, 1 ovarian) from CSF (19% success rate compared to approximately 33% for solid tumors) and matched cell lines from the resulting PDX tissues. Intracardiac injection of HMSC-RET cells resulted in tumors establishing in several peripheral organs and the brain. SUMMARY AND CONCLUSIONS We have established disease models of CNS metastasis and LMD. Translational studies where patients with clinical suspicion of LMD undergo CSF sampling, NGS/ctDNA analysis, and PDX modeling are crucial in improving our understanding of this metastatic compartment and investigating novel treatment paradigms. Future studies will be focused on examining the biochemical and genetic nature of these tumors as well as developing effective therapeutic strategies.

Intra-Articular Injections of the Adipose-Derived Mesenchymal Stem Cells Suppress Progression of a Mouse Traumatic Knee Osteoarthritis Model.

This study aimed to determine whether the intra-articular injection of human adipose-derived mesenchymal stem cells (ADSCs) protects against the progression of murine post-traumatic osteoarthritis. ADSCs were isolated from human abdomen or buttock adipose tissues. In in vitro study, ADSCs conditioned medium was added to human chondrocytes pre-treated with interleukin-1β (IL-1β), and resultant gene expression of target inflammatory genes was measured by real-time quantitative polymerase chain reaction. A mouse model of knee osteoarthritis was generated by unilaterally transecting the medial meniscus in the right hind limb of 20 female C57BL/6 mice. Mice were randomly assigned to 2 treatment groups that received 6 µl intra-articular injections of either phosphate-buffered saline (control) or 2 × 104 cells/μl of ADSCs 14, 28, and 42 days post-surgery. Mice were euthanized 84 days post-surgery and histological and micro-computed tomography evaluation of knee joints were analyzed. Hind limb weight-bearing distribution was measured pre-surgery and 28 and 84 days post-surgery. Conditioned medium from cultured human adipose-derived mesenchymal stem cells suppressed the expression of target inflammatory genes in chondrocytes pre-treated with IL-1β, suggesting anti-inflammatory properties (P < 0.01). Histological analyses indicated that the progression of destabilization of medial meniscus-induced knee osteoarthritis was suppressed by the administration of ADSCs compared with control group at medial femorotibial joint in vivo. This protective effect was related to a reduction in articular cartilage loss. The intra-articular injection of ADSCs suppressed articular cartilage loss in a mouse model of knee osteoarthritis, possible through anti-inflammatory mechanisms.

Current state of the art in hypoplastic left heart syndrome.

Hypoplastic left heart syndrome (HLHS) is a complex congenital heart condition in which a neonate is born with an underdeveloped left ventricle and associated structures. Without palliative interventions, HLHS is fatal. Treatment typically includes medical management at the time of birth to maintain patency of the ductus arteriosus, followed by three palliative procedures: most commonly the Norwood procedure, bidirectional cavopulmonary shunt, and Fontan procedures. With recent advances in surgical management of HLHS patients, high survival rates are now obtained at tertiary treatment centers, though adverse neurodevelopmental outcomes remain a clinical challenge. While surgical management remains the standard of care for HLHS patients, innovative treatment strategies continue to be developing. Important for the development of new strategies for HLHS patients is an understanding of the genetic basis of this condition. Another investigational strategy being developed for HLHS patients is the injection of stem cells within the myocardium of the right ventricle. Recent innovations in tissue engineering and regenerative medicine promise to provide important tools to both understand the underlying basis of HLHS as well as provide new therapeutic strategies. In this review article, we provide an overview of HLHS, starting with a historical description and progressing through a discussion of the genetics, surgical management, post-surgical outcomes, stem cell therapy, hemodynamics and tissue engineering approaches.

Clinical efficacy and safety of the combination of mesenchymal stem cells and scaffolds in the treatment of knee osteoarthritis: Protocol for systematic review and meta-analysis.

Mesenchymal stem cells (MSCs) injection combined scaffolds for knee osteoarthritis (OA) is a relatively new treatment for knee OA and has not yet gained popularity. So, the effectiveness, safety is worthy to be explored. We performed a protocol for systematic review and meta-analysis to evaluate the efficacy and safety of the combination of MSCs and scaffolds in the treatment of knee OA. A literature search was performed in October 2022 without restriction to regions, publication types or languages. The primary sources were the electronic databases of PubMed, EMBASE, Cochrane Library, Web of Science and the ClinicalTrials.gov. Risk of bias was assessed using the Cochrane Collaboration's risk of bias tool for randomized controlled trials. Statistical analyses were performed utilizing Review Manager 5 (The Nordic Cochrane Center, Copenhagen, Denmark). Visual analog scale score, Western Ontario and McMaster Universities Osteoarthritis Index, Lysholm knee scale and adverse events will be assessed. The systematic review will provide evidence to assess the effectiveness and safety of MSCs combined scaffolds for the treatment of knee OA.

Intervention effects of traditional Chinese medicine on stem cell therapy of myocardial infarction.

Cardiovascular diseases are the leading cause of global mortality, in which myocardial infarction accounts for 46% of total deaths. Although good progress has been achieved in medication and interventional techniques, a proven method to repair the damaged myocardium has not yet been determined. Stem cell therapy for damaged myocardial repair has evolved into a promising treatment for ischemic heart disease. However, low retention and poor survival of the injected stem cells are the major obstacles to achieving the intended therapeutic effects. Chinese botanical and other natural drug substances are a rich source of effective treatment for various diseases. As such, numerous studies have revealed the role of Chinese medicine in stem cell therapy for myocardial infarction treatment, including promoting proliferation, survival, migration, angiogenesis, and differentiation of stem cells. Here, we discuss the potential and limitations of stem cell therapy, as well as the regulatory mechanism of Chinese medicines underlying stem cell therapy. We focus on the evidence from pre-clinical trials and clinical practices, and based on traditional Chinese medicine theories, we further summarize the mechanisms of Chinese medicine treatment in stem cell therapy by the commonly used prescriptions. Despite the pre-clinical evidence showing that traditional Chinese medicine is helpful in stem cell therapy, there are still some limitations of traditional Chinese medicine therapy. We also systematically assess the detailed experimental design and reliability of included pharmacological research in our review. Strictly controlled animal models with multi-perspective pharmacokinetic profiles and high-grade clinical evidence with multi-disciplinary efforts are highly demanded in the future.

S191 Efficacy and Safety of Adipose-Derived Stem Cell Therapy for the Treatment of Complex Perianal Fistula Not Associated With Crohn’s Disease: A Systematic Review and Meta-Analysis

Introduction: Given the high recurrence rate and the risk of fecal incontinence with surgical options, Injection of adipose tissue-derived stem cells (ASC) has been arising as a novel method for treating complex perianal fistulas (CPAF). Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of ASC in the management of CPAF not associated with Crohn’s disease. Methods: We systematically searched Medline and Embase databases through April 20, 2022, for all studies that assessed the efficacy and safety of ASC for the treatment of CPAF not associated with Crohn’s disease. We excluded patients with rectovaginal fistulas and perianal fistulas associated with Crohn’s disease. Our primary outcome was the complete closure. The secondary outcomes included overall nonserious adverse events (NSAE), serious adverse events (SAE), and perianal abscess rate. All meta-analyses were conducted using a random-effect model. The publication bias was assessed by Egger’s test. Results: Ten studies (eight clinical trials and two observational studies) with 271 patients were included in the pooled analysis. Eight studies used autologous stem cells, one used allogeneic stem cells, and one did not report the source of stem cells. The mean age of the patients was 43.7 years. The follow-up period ranged from 3 months to 2 years. The pooled complete closure rate was 59.7% (95% confidence interval (CI): 0.46-0.73, Figure 1A). On subgroup analysis based on country of origin, six studies with 213 patients were conducted in European countries, and four studies with 58 patients were conducted in non-European countries. The complete closure rate was higher in European countries than non-European countries, 64.1% vs. 52.6%. Eight studies reported overall NSAEs with the pooled NSAE rate of 22.5% (95% CI: 0.11-0.34, Figure 1B). Seven studies reported SAEs with the pooled SAE rate of 1.7% (95% CI: 0.001-0.034, Figure 1C). Seven studies reported the perianal abscess rate with a pooled perianal abscess rate of 7.1% (95% CI: 0.016-0.125, Figure 1D). No evidence of publication bias was found (Egger’s test: P=0.36). Conclusion: Our meta-analysis demonstrated that ASC is a promising therapeutic option for CPAF not associated with Crohn’s disease with a clinically adequate efficacy and low rate of adverse events. However, more studies with larger sample sizes are needed to provide a definitive assessment of the effectiveness of ASCs for CPAF not associated with Crohn’s disease.Figure 1

Mesenchymal Stem Cells Treatment Aggravates Tumor Growth Regardless Its Route of Administration: An In vivo Study.

to clarify the effect of MSCs in cancer growth and to detect whether the rout of administration (either locally inside the tumor tissue or systemic )could affect the outcome of treatment or not. Eighteen female mice were involved in the study. All mice were subcutaneously inoculated with Ehrlich tumor cells into the right flank. After three week of tumor growth; the mice were divided randomly in to three groups six mice for each ; group I: untreated Erlish tumor group; group II: Erlish tumor treated by local injection of 1 x106 MSCs/week inside the tumor tissue, group III: Erlish tumor treated by systemic injection of 1 x106 MSCs iv in tail vein/week. Tumor growth was recorded .After 4 weeks of stem cells injection, all rats were sacrificed by cervical dislocation and tumor tissues were collected for histopathological study. inflammatory cytokine TNF was assessed by ELISA, lncRNA MALAT ,NFKB and MMP2 genes expression were assessed by Quantitative RT-PCR. Erlish tumor was developed as a well-defined capsule composed by connective tissue infiltrated by inflammatory and neoplastic cells surrounded the tumors. The tumor growth regarding size and weight of tumor tissue was significantly aggravated after both local and systemic treatment MSCs (p value =0.007, 0.001) respectively. Inflammatory cytokines TNF and NFKB were significantly elevated (p value <0.0001), lncRNA MALAT, MMP2 expressions were significantly induced (p value <0.0001), after MSCs treatment with more significant increase in those treated by local intratumor injection of MSCs compared to those treated by systemic MSCs(p value <0.0001). Ehrlich tumor model is feasible and easily monitored tumor model. Although MSCs have anti-inflammatory effect and the ability to regenerate the damaged tissue; it could aggravate tumor growth as it exploited by cancer cells for behave of tumor cells.

S3219 Acute Hepatitis C After Penile Stem Cell Injection

S3219 Acute Hepatitis C After Penile Stem Cell Injection

3D Printed Total Talus Replacement after Free Vascularized Medial Femoral Condyle Osteocutaneous Flap for Avascular Necrosis of the Talus Leads to Poor Clinical Outcomes

Category: Hindfoot Introduction/Purpose: Talar avascular necrosis (AVN) is a difficult pathology to diagnose and manage. Traditional treatment options include both joint sparing procedures (vascularized bone graft, core decompression, intraosseous stem cell injection) and joint sacrificing procedures (arthrodesis or arthroplasty). Three dimensional (3D) printed total talus replacement (TTR) has recently gained more popularity as an intervention to salvage joint motion in patients with talus pathology. Although vascularized bone grafting can treat localized talar AVN, failure of this procedure to improve talar vascularity and prevent further subchondral collapse may require revision surgery. This is the first study to compare outcomes of patients with talar AVN who underwent primary 3D printed TTR and patients who underwent a secondary TTR subsequent to failure of a free vascularized medial femoral condyle (MFC) flap. Methods: This case series analyzed the outcomes of two patients who underwent a secondary 3D printed TTR subsequent to failure of the index revascularization procedure using an MFC flap in 2016. These patients were compared to a cohort of patients who underwent a primary 3D printed TTR to treat talar AVN between 2016 and 2019. Preoperative and postoperative assessment included ankle range of motion, foot and ankle outcome score (FAOS), visual analogue scale (VAS) pain scores, and radiographic imaging. A minimum 12-month follow-up period was reported for patients. Results: Within the group that underwent a secondary TTR after a failed revascularization, both patients had a mean followup of 23.5 months. The 25 patients in the comparison group who all underwent a primary 3D printed TTR had an mean follow-up period of 22.1 (range:12-43) months. All patients in the study experienced improved VAS pain scores and ankle dorsiflexion post- operatively. In the secondary 3D printed TTR group, both patients demonstrated reduced plantarflexion of 20 degrees and ankle motion of 15 degrees relative to the comparison group which showed a minimal increase in both. When analyzing FAOS functional outcome score subscales, patient two demonstrated improvement in pain from 44 to 46, symptoms from 29 to 46, and activities of daily living from 47 to 76. Patient one experienced a decrease in sports and recreation from 15 to 5 and quality of life from 38 to 31. Conclusion: This case series demonstrated poor functional outcomes of two patients who underwent 3D printed TTR after talar revascularization with MFC grafts when compared to the cohort of patients who solely underwent a primary 3D printed TTR for talar AVN. Further investigation is warranted to determine which patients may benefit from a revascularization procedure or a primary 3D printed TTR.

Acute Local Reaction after Intra-Articular Infiltration and Implantation of Microfragmented Autologous-Adipose Tissue (MFAT) - A Case Report

Adipose Tissue (AT) has become a source of Mesenchymal Stem/Stromal Cells (MSC) for regenerative medicine applications, particularly in musculoskeletal disorders.The MFAT is a potent point of care regenerative therapy as a local treatment by intra-articular injection and implantation of mesenchymal stem cells, with the aim of improving degenerative osteoarthritis of the knee and other musculoskeletal conditions

Liver repair of NAFLD patients following effortless exercise and the possible involvement of endogenous stem cells

Adipose tissue derived stem cells differentiate into mesenchymal stem cells (MSCs) and hepatocytes which are involved in anti-inflammatory, reparatory, and detoxification processes reinstating liver function. Aerobic, resistance and effortless workouts have been proven to be beneficial for patients with NAFLD, possibly due to stem cells released into the bloodstream from metabolized fat during exercise induced natural lipolysis. We analysed the serum levels of a number of variables such as ALT, AST, ALP, albumin, creatinine, bilirubin, triglycerides and CRP to determine if effortless exercise would demonstrate an improvement of the NAFLD condition that is substantially equivalent to liver repair documented after administering exogenous MSCs injections. We examined 10 prediabetic individuals with NAFLD, 5 males and 5 females 54-64 years of age, who received 15 treatments with an effortless exercise technology, originally invented at London University for obese individuals who have difficulty performing strenuous workouts, as well as those with limited mobility due to age or disease. The hypothesis was that the reduction of triglycerides and visceral adipose tissue (VAT) is accompanied by a natural release of adipose tissue contents into the bloodstream, supplying endogenous MSCs that differentiate into hepatocytes necessary for healthy liver functioning. Results demonstrated a statistically significant improvement of the NAFLD condition in ultrasonography reports along with optimal levels of ALT, AST, ALP, albumin, creatinine, bilirubin and CRP. Additional findings included a notable decrease in triglycerides, VLDL, BMI, VAT, and cortisol, accompanied by an increase in testosterone, BMR, and muscle mass. Our results replicated previous studies which documented a significant repair of hepatic steatosis in ultrasonography reports after using this effortless exercise regimen. The current clinical study strongly suggested the involvement of endogenous MSCs that are vital in organ repair. Reducing VLDL, VAT and triglycerides optimizes health, setting the conditions for the reparative process to commence. The possibility of endogenously released MSCs as a result of an exercise method is a new perspective with very little past research, therefore, more clinical studies focusing on this hypothesis are warranted. Demonstrating the production of endogenous MSCs via an exercise modality will introduce novel treatments for metabolic disorders without the adverse effects often observed after stem cells injections or invasive and trauma based procedures.

Efficacy of Intra-Articular Injection of Platelet-Rich Plasma Combined with Mesenchymal Stem Cells in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

Objective This study systematically evaluated the effect of intra-articular injection of platelet-rich plasma (PRP) and mesenchymal stem cells (MSC) on knee osteoarthritis (KOA). Methods Randomized controlled trials (RCTs) of PRP combined with MSC in the treatment of KOA were collected from PubMed, Cochrane Library, Web of Science, Wiley online library, CNKI, and Wanfang databases from inception to July 30, 2022. Two researchers read and screened the literature to extract the data, respectively. After conducting a risk-of-bias assessment of included data, RevMan 5.3 software was used for meta-analysis. The Cochrane Handbook risk-of-bias assessment tool was used to evaluate the included literature. Results A total of 9 papers with 480 KOA patients were included in this study. Significant differences in terms of visual analogue scale (VAS) score (MD = −1.10, 95% CI −1.91 to −0.29), P = 0.008) and knee injury and osteoarthritis outcome score (KOOS) (MD = 4.56, 95% CI 0.54–8.58, P = 0.050) were noted between the 2 groups. Subgroup analysis found that MD = 1.66 in KOOS-pain-1 group (95% CI (0.10, 3.22), P = 0.040), which is significant. The MD for KOOS total score and IKDC scores between the two groups was MD = 6.31 (95% CI 2.73–9.88, P = 0.0005) and MD = 3.05 (95% CI −7.09–13.20, P = 0.56), respectively. Conclusion The results of this study provide a theoretical basis for the clinical treatment of KOA with PRP combined with MSC.

Intra-arterial injection of mesenchymal stem cells to accelerate neointima formation after endovascular stenting in a rabbit model.

Delayed neointima formation over a neurovascular stent is associated with thrombotic complications that can lead to stroke. The purpose of this study was to evaluate whether an intra-arterial injection of mesenchymal stem cells (MSCs) after stent placement leads to improved neointima and reduced thrombus formation over the device. Solitaire stents were placed into the aortas of rabbits that were divided into MSC and control groups. The MSC group received an intra-arterial injection of MSCs through the same microcatheter used for stent deployment. Optical coherence tomography (OCT) was used to evaluate and compare neointima and thrombus formation in a blinded fashion. Explanted specimens were also imaged with scanning electron microscopy (SEM) and evaluated by observers blinded to group allocation using an endothelialization scoring system. The 3-day MSC group was similar to the 7-day controls in terms of stent strut coverage ratio and maximum neointimal thickness, but these values were significantly higher than the 3-day control group based on a hierarchical mixed-effects linear regression analysis. SEM revealed a significantly higher endothelialization score for the MSC group compared with controls at the same time point. There was no difference in thrombus formation between any of the groups. The intra-arterial injection of MSCs after endovascular stenting accelerated early neointima formation but had no effect on thrombus formation in this study. Larger studies are required to verify these findings and determine the durability and mechanism of this effect.

Caffeic Acid Phenethyl Ester With Mesenchymal Stem Cells Improves Behavioral and Histopathological Changes in the Rat Model of Parkinson Disease.

Parkinson disease (PD) results from the destruction of dopaminergic neurons in the brain. This study aimed to investigate the protective effects of natural antioxidants such as caffeic acid phenethyl ester (CAPE) to maintain these neurons. CAPE is one of the main ingredients of propolis. Intranasal administration of 1-methyl-4-phenyl-2;3;4;6-tetrahydropyridine (MPTP) was used to generate a PD model in rats. A total of 2×bone marrow stem cells (BMSCs) were injected from the tail vein. Behavioral tests, immunohistochemistry, DiI, cresyl fast violet, and TUNEL staining were used to evaluate the rats 2 weeks after treatment. In all treatment groups with stem cells, the DiI staining method revealed that the cells migrated to the substantia nigra pars compacta after injection. Treatment with CAPE significantly protects dopaminergic neurons from MPTP. The highest number of tyrosine hydroxylase (TH) positive neurons was seen in the pre-CAPE+PD+stem cell (administration of CAPE, then the creation of PD, finally injection of stem cells) group. The number of TH+cells in all groups that received CAPE was significant compared to groups that received the stem cells only (P<0.001). Intranasal administration of MPTP significantly increases the number of apoptotic cells. The lowest number of apoptotic cells was in the CAPE+PD+stem cell group. The results showed that the use of CAPE and stem cells in Parkinson rats caused a significant reduction in the apoptotic cells.

Can mobilization of bone marrow stem cells be an alternative regenerative therapy to stem cell injection in a rat model of chronic kidney disease?

Chronic kidney disease (CKD) is a priority health problem affecting 36% of Egyptians. Adipose‐derived mesenchymal stem cells (ADMSCs) have multidifferentiation capacity and the ability to restore several types of cells including damaged renal cells. Granulocyte colony‐stimulating factor (G‐CSF) is known to mobilize hematopoietic stem cells from bone marrow to the peripheral circulation. The aim of this study was to compare the effect of endogenous CD34+ cells mobilization and exogenous ADMSCs administration in the treatment of a rat model of adriamycin (ADR)‐induced CKD. A total of 48 male albino rats of the local strain (200 ± 50 g) were equally divided into four groups: control negative, ADR (control positive), ADMSCs group, and G‐CSF group. Six rats from each group were sacrificed after 4 weeks and the other 6 after 12 weeks. Renal function was assessed frequently by measuring serum creatinine, albumin, urea, 24‐h urinary protein level, and hemoglobin level throughout the study. Oxidative stress markers malondialdehyde (MDA) and total antioxidant (TAO) were measured on day 28. CD‐34+ cell percentage was measured on day 9. After the sacrification of the rats, kidneys were removed for histopathological assessment. Results revealed that both ADMSCs and G‐CSF significantly improved serum creatinine, albumin, urea, 24‐h urinary protein level, and histopathological damage score, with the G‐CSF‐treated group showing better improvement in 24‐h urinary protein level, serum albumin, and histopathological damage score compared with ADMSCs‐treated group. The G‐CSF group also had significantly higher levels of CD34+ cells. Oxidative stress markers (MDA and TAO) levels were significantly improved with both therapies. We conclude that mobilization of endogenous hematopoietic stem cells by G‐CSF is more effective than exogenously injected ADMSCs in protecting the kidneys against AD‐induced toxicity.

Safety and feasibility of intramedullary injected bone marrow-derived mesenchymal stem cells in acute complete spinal cord injury: phase 1 trial.

The intramedullary route holds the potential to provide the most concentration of stem cells in cases of spinal cord injury (SCI). However, the safety and feasibility of this route need to be studied in human subjects. The aim of this study was to evaluate the safety and feasibility of intramedullary injected bone marrow-derived mesenchymal stem cells (BM-MSCs) in acute complete SCI. In this prospective study conducted over a 2-year period, 27 patients with acute (defined as within 1 week of injury) and complete SCI were randomized to receive BM-MSC or placebo through an intramedullary route intraoperatively at the time of spinal decompression and fusion. Institutional ethics approval was obtained, and informed consent was obtained from all patients. Safety was assessed using laboratory and clinicoradiological parameters preoperatively and 3 and 6 months after surgery. A total of 180 patients were screened during the study period. Of these, 27 were enrolled in the study. Three patients withdrew, 3 patients were lost to follow-up, and 8 patients died, leaving a total of 13 patients for final analysis. Seven of these patients were in the stem cell group, and 6 were in the control group. Both groups were well matched in terms of sex, age, and weight. No adverse events related to stem cell injection were noted for laboratory and radiological parameters. Five patients in the control group and 3 patients in the stem cell group died during the follow-up period. Intramedullary injection of BM-MSCs was found to be safe and feasible for use in patients with acute complete SCI.

Major clinical findings of cellular therapy for intravitreal use in ischemic retinopathy and macular degeneration: a systematic review

Introduction: In the scenario of eye diseases, diabetic retinopathy and retinal vein occlusion are the two most common ischemic retinopathies in the world. Ischemia is caused by retinal vascular diseases due to decreased blood perfusion and the appearance of areas of retinal non-perfusion. Also, age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in people over 65 years of age in industrialized countries. By 2020, around 200 million people will be affected by AMD worldwide. Objective: the present systematic review study aimed to highlight the main clinical findings of the treatment of ischemic retinopathy and age-related macular degeneration through cell therapy with bone marrow stem cells. Methods: The rules of the Systematic Review-PRISMA Platform were followed. The search was carried out from March 2022 to June 2022 in Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument. The risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: It was found 235 articles involving retinitis pigmentosa, macular degeneration, and bone marrow stem cell therapy. A total of 51 were fully evaluated and 28 studies were included and developed in a systematic review in the results field. The symmetrical Funnel Plot does not suggest a risk of bias between the small sample size studies. It was concluded that intravitreal injection of bone marrow-derived stem cells in a patient with retinal vascular occlusion sequelae demonstrated that the procedure is feasible and safe to be performed in humans as there were no signs of infection, inflammation, or development of intraocular tumor formation. Also, neurotrophic effects correlate with vasculature preservation, suggesting that bone marrow-derived stem cells can be used in the treatment of diseases such as retinal degenerations and vasculopathy that currently lack effective treatment. The authors concluded that stem cells can protect retinal cells from degeneration and also suggested that they were able to replace some types of lost retinal neurons.

Preventive effects of bone marrow-derived mesenchymal stem cell transplantation in a D-galactose-induced brain aging in rats.

Aging is a complex process accompanied by numerous morphological, functional, and metabolic impairments in the brain, and a critical risk factor involved in the increasing incidence of neurodegenerative diseases. Few studies have evaluated the efficacy of different sources of mesenchymal stem cells (MSCs) in ameliorating the early morphological and functional alterations in the aging brain. This study, for the first time, evaluated the potential efficacy of intravenous injection of bone marrow-derived mesenchymal stem cells (BMMSCs) in a D-galactose-induced rat model of brain aging. BMMSCs (1 × 10⁶) were intravenously injected into brain aging model rats once every 2 weeks for 8 weeks. The transplanted cells survived and migrated to the brain, and differentiated into astrocytes and neurons, including choline acetyltransferase neurons. BMMSC transplantation improved locomotor activity and cognitive functions, restored cholinergic system function, protected atrophic cholinergic neurons in the basal forebrain, induced antioxidative effects and restored neurotrophic factors, and modulated hippocampal synaptic plasticity by upregulating PSD95 and Egr1 expression. Our findings demonstrated the efficacy of BMMSC injection in an aging rat model and suggest that these cells may be developed into an effective cell therapy for the aging brain.

Management of perianal fistulas in Crohn's disease: a 2021 update of the French National Society of Coloproctology consensus.

Since our last publication of algorithms for the management of perianal fistulas in patients with Crohn's disease, researchers have proposed a treat to target strategy systematic combotherapy for anal lesions, and indications for stem cell injection. In the absence robust publications, the Société Nationale Française de Coloproctologie (French National Society of Coloproctology [SNFCP]) wished to establish a group consensus using the Delphi method. From October 2020 to January 2021, a scientific committee and panel of gastroenterologists and surgeons established answers which were submitted to the members of the SNFCP during a national conference in November 2020. Three questions were clarified and reformulated, and then submitted during a third and final round of consultation of members of the SNFCP. The target was defined as being the response obtained in every domain (symptoms, physical and radiological evaluation) which could be considered satisfactory, without the need to intensify therapeutic management. By consensus, the time required for clinical evaluation of the efficacy of treatment was 6months. A response on magnetic resonance imaging (MRI) should include the absence of a collection of 10mm or more in size at 6months, and a frank decrease or complete disappearance of hyperintensity in T1 and T2 sequences of the main tract at 12months. Systematic association of an immunosuppressant with tumor necrosis factor inhibitors did not reach the consensus level for adalimumab (50%), but just did for infliximab (70%). The majority of the respondents considered failure of one, or even two lines of different biotherapies to be potential indications for injection of stem cells. These findings reinforce the importance of composite targets including MRI evaluation, and underscore the need for precise timing of evaluation. Combotherapy is only recommended with infliximab. Injection of stem cells is a second- or third-line option.

The Use of 3D Polylactic Acid Scaffolds with Hydroxyapatite/Alginate Composite Injection and Mesenchymal Stem Cells as Laminoplasty Spacers in Rabbits.

Several types of laminoplasty spacer have been used to fill bone gaps and maintain a widened canal. A 3D scaffold can be used as an alternative spacer to minimize the risk observed in allografts or autografts. This study aims to evaluate the in vivo biocompatibility and tissue–scaffold integration of a polylactic acid (PLA) scaffold with the addition of alginate/hydroxyapatite (HA) and mesenchymal stem cell (MSc) injections. This is an experimental study with a pretest and post-test control group design. A total of 15 laminoplasty rabbit models were divided into five groups with variations in the autograft, PLA, HA/alginate, and MSc scaffold. In general, there were no signs of inflammation in most samples (47%), and there were no samples with areas of necrosis. There were no significant differences in the histopathological results and microstructural assessment between the five groups. This demonstrates that the synthetic scaffolds that we used had a similar tissue reaction and tissue integration profile as the autograft (p > 0.05). We recommend further translational studies in humans so that this biocompatible fabricated scaffold can be used to fill bone defects.