Fetal Stem Cell Transplantation Research Articles

Embryonic vitamin D deficiency programs hematopoietic stem cells to induce type 2 diabetes

Environmental factors may alter the fetal genome to cause metabolic diseases. It is unknown whether embryonic immune cell programming impacts the risk of type 2 diabetes in later life. We demonstrate that transplantation of fetal hematopoietic stem cells (HSCs) made vitamin D deficient in utero induce diabetes in vitamin D-sufficient mice. Vitamin D deficiency epigenetically suppresses Jarid2 expression and activates the Mef2/PGC1a pathway in HSCs, which persists in recipient bone marrow, resulting in adipose macrophage infiltration. These macrophages secrete miR106-5p, which promotes adipose insulin resistance by repressing PIK3 catalytic and regulatory subunits and down-regulating AKT signaling. Vitamin D-deficient monocytes from human cord blood have comparable Jarid2/Mef2/PGC1a expression changes and secrete miR-106b-5p, causing adipocyte insulin resistance. These findings suggest that vitamin D deficiency during development has epigenetic consequences impacting the systemic metabolic milieu.

Clinical Outcomes of Fetal Stem Cell Transplantation in Type 1 Diabetes Are Related to Alternations to Different Lymphocyte Populations.

Background: In patients with diabetes, transplantation of stem cells increases C-peptide levels and induces insulin independence for some period. Today, this positive therapeutic outcome is widely attributed to the well-documented immunomodulatory properties of stem cells. The aim of this study was to report alternations (the trend of increase or decrease) in different lymphocyte populations in a stem cell clinical trial performed in our institute. Methods: Recorded data of a clinical trial conducted on 72 patients with type 1 diabetes who had received fetal stem cell transplantation several years ago and were regularly monitored before and after the procedure in 1, 3, 6, 12, 24 months were analyzed. In these regular follow-up visits, insulin demand, HbA1c, C-peptide, and alternation to B cell and T cell populations were analyzed and recorded. For the purpose of the current study, patients were retrospectively divided into 2 groups, namely, those with the positive response to treatment and patients without such response. Temporary positive therapeutic response was defined by 2 different indicators, namely, plasma C-peptide levels and insulin dose-adjusted A1C (IDAA1c), which was calculated as A1C (percent) + (4 × insulin dose (units per kilogram per 24 h). Data analysis was performed by means of SPSS Version 18. Results: Besides the short-term therapeutic effect, we observed remarkably significant alternations to the populations of B and T lymphocytes in the recipients. When patients were retrospectively assigned to 2 different groups of patients with a positive therapeutic response (based on C-peptide changes) and those without it, it was observed that alternations to different populations of B-cells and T-cells were significantly different in these 2 groups. Conclusion: Our results demonstrated that transplantation of stem cells leads to significant positive therapeutic outcomes in one group of patients who showed totally distinct patterns of alternation to different groups of lymphocytes.

P.102: Long Term Outcomes After Fetal Pancreatic Stem Cell Transplantation in Diabetes Mellitus: Data From Unified National Electronic Health System 2014–2019

Introduction: Fetal pancreatic stem cell transplantations (FPCT) from the aborted fetuses of 16–20 weeks gestation have been approved for the treatment of diabetes mellitus (DM) in a single tertiary research and training hospital in Kazakhstan. Although the immediate short-term beneficial effect was observed, there was a lack of long-term mortality assessment and the risk of diabetes-related complications among patients receiving FPCT compared to patients receiving conventional treatment (CT). We aimed to study long-term all-cause mortality and diabetes-related complications in DM patients who underwent EPCT versus CT using large-scale administrative health data from Unified National Electronic Health System (UNEHS). Methods: The initial cohort of 102,611 patients who were admitted to the hospital with DM were identified using ICD-10 codes through UNEHS between 2014–2019. Out of them, 504 patients who underwent FPCT were defined using ICD-9 procedure codes. Mortality data and patient-related demographics were linked from the National Population Registry. Identified datasets were cross-checked with the whole UNEHS dataset (n=1,565,093 observations) to ascertain the following complications/comorbidities: coronary heart disease (CHD), stroke, retinopathy, nephropathy, neuropathy, diabetic foot, neoplasms. Based on patients’ baseline characteristics (age, sex, duration of DM, residency, ethnicity, number of hospitalizations, and type of diabetes), the cohort of FPCT patients (n=504) matched with a cohort of CT patients (n=102,611) with a 1:5 ratio by propensity score matching (PSM). The final cohort of 2847 patients (504 with EPCT vs 2,343 with CT) was further evaluated. Results: After PS matching, baseline characteristics for FPCT and CT groups did not differ. Median (IQR) age was 50.6 (41.5–57.4) years old and the median duration of diabetes accounted for 6.3 (4.7–10.7) years. The cohort consisted of 55.4% females, 75.2% Kazakhs, 85.3% of type 2 DM, and 72.2% of urban residents. The median number of hospitalizations in 2014–2019 was 3 (1–6). The results of diabetes-related events and all-cause mortality presented in table 1.In logistic regression analysis, FPCT group had 48% lower risk of all-cause death compared to CT group (Odds Ratio 0.52; 95%CI: 0.37–0.72; p-value <0.001). Also, those DM patients receiving FPCT compared to the CT group were less likely to experience CHD, diabetic retinopathy, neuropathy, and diabetic foot, however, they were more likely to have diabetic nephropathy. There was no difference between the groups in terms of stroke and cancer incidences. Survival analysis depicted in figure 1.Conclusion: Findings suggest that patients receiving FPCT had a 48% lower risk of all-cause death. We also reveal better outcomes for the FPCT group regarding CHD, retinopathy, nephropathy, neuropathy, and diabetic foot, however, the EPCT group had a higher risk of nephropathy. Further investigations involving clinical and laboratory data are warranted. This study was supported by grants from the Nazarbayev University Faculty Development Research Grant Program FDCRGP 2020–2022 (Funder Project Reference: 240919FD3913).

Treatments Being Developed in Retinitis Pigmentosa

Recent developments in understanding the pathophysiology of retinitis pigmentosa (RP) have shown that there have been new hopes in the treatment of this disease which can cause severe vision loss. Proven therapy for RP-associated photoreceptor loss and retinal pigment epithelial damage has not yet been reported. New or experimental approaches for the treatment of RP include platelet-rich plasma, gene therapy, transplantation of fetal retinal cells or stem cells, and electronic retinal prostheses.

Assessment of immune-alternations and their correlations with therapeutic outcomes of transplantation of autologous Mesenchymal and Allogenic fetal stem cells in patients with type 1 diabetes: a study protocol.

Stem-cell therapy, which has recently emerged as a potentially therapeutic option for diabetes, is demonstrated to significantly alter both cellular and non-cellular elements of the immune system. In addition, it is demonstrated that allogenic stem-cells, once considered immune-privileged, can be rejected by the host immune system almost similar to any other somatic cell. To date, nonetheless, details of these intricate interactions remain obscure. The current study is designed to illuminate both aforementioned favorable and unfavorable stem cell-mediated immune reactions. Findings of this study may shed some light on how stem cells may exert their therapeutic effect in type 1 diabetes through immune system-mediated mechanisms and illuminate the partially-obscure immune-caused rejection of these cells. For the purpose of this study, frozen whole blood samples obtained from patients with type 1 diabetes who received stem cells at the Endocrinology and Metabolism Research Institute of Tehran University of Medical Sciences in two different clinical trials will be thawed and analyzed. These clinical trials were carried out using two different sources of stem cells, namely allogenic fetal and autologous mesenchymal cells. The samples we aim to analyze were obtained from the patients before the procedure and regularly after it, one, three, six, 12, and 24months later. For the purpose of this study, the following parameters will be measured: C-peptide levels, IDAA1c (a surrogate marker of beta cell function which is calculated as HbA1c (%) + [4 × insulin dose (units per kilogram per day)]), frequencies of islet-specific autoreactive CD8+ T cells (CTL), different lymphocyte subsets, thymic function indicators, T cell repertoire diversity (including Treg/Tconv ratios), plasma levels of several pro- and anti-inflammatory cytokines, diabetes autoantibodies, and HLA typing. The stem cell transplantation clinical trials which provided the primary source of our samples were carried out at the Endocrinology and Metabolism Research Institute of Tehran University of Medical Sciences between 2008 and 2012. These series of clinical trials have secured approval of the ethics committee of Tehran University of Medical Sciences (ethical code number: E-0089) and registered on the national clinical trial registry of Islamic Republic of Iran (IRCT) with the identifier codes: IRCT138810271414N8 (for autologous mesenchymal cells) and IRCT201103171414N23 (for allogenic fetal cells). Our findings are to be presented at international scientific events, published in peer-reviewed journals, and disseminated both electronically and in print. Besides, results of the current study will be used for design and implementation of future laboratory investigations and clinical trials at the Endocrinology and Metabolism Research Institute of Tehran University of Medical Sciences.

Effect of Transplantation of Neural Stem and Progenitor Cells on Memory in Animals with Alzheimer's Type Neurodegeneration.

The effects of systemic and intracerebral transplantation of human fetal neural stem and progenitor cells were studied on the model of olfactory bulbectomy in mice with developing signs of sporadic Alzheimer's disease. It was found that transplantation of these cells at certain stages of disease development contributed to improvement of spatial memory and preservation of hippocampal neurons in these animals.

Fetal liver stem cell transplantation for liver diseases.

Stem cell transplantation exhibited a promising lifesaving therapy for various end-stage liver diseases and could serve as a salvaging bridge until curative methods can be performed. In past decades, mature hepatocytes, liver progenitor cells, mesenchymal stem cells and induced pluripotent stem cells have been practiced in above settings. However, long-term survival rates and continuous proliferation ability of these cells in vivo are unsatisfactory, whereas, fetal liver stem cells (FLSCs), given their unique superiority, may be the best candidate for stem cell transplantation technique. Recent studies have revealed that FLSCs could be used as an attractive genetic therapy or regenerative treatments for inherited metabolic or other hepatic disorders. In this study, we reviewed current status and advancements of FLSCs-based treatment.

Stakeholder views and attitudes towards prenatal and postnatal transplantation of fetal mesenchymal stem cells to treat Osteogenesis Imperfecta

The Boost Brittle Bones Before Birth (BOOSTB4) clinical trial is investigating the safety and efficacy of transplanting fetal derived mesenchymal stromal cells (MSCs) prenatally and/or in early postnatal life to treat severe Osteogenesis Imperfecta (OI). This study aimed to explore stakeholder views to understand perceived benefits or concerns, identify ethical issues and establish protocols for support and counselling. Semi-structured qualitative interviews were conducted with three groups; 1. Adults affected with OI, with and without children, and parents of children affected with OI; 2. Health professionals who work with patients with OI; 3. Patient advocates from relevant patient support groups. Interviews were digitally recorded, transcribed verbatim and analysed using thematic analysis. Interviews with 56 participants revealed generally positive views towards using fetal MSC transplantation to treat OI. Early treatment was considered advantageous for preventing fractures and reducing severity and could bring psychological benefits for parents. Common concerns were procedure safety, short/long-term side effects and whether transplantation would be effective. Difficulties inherent in decision-making were frequently discussed, as treatment efficacy is unknown and, by necessity, parents will make decisions at a time when they are vulnerable. Support needs may differ where there is a family history of OI compared to an unexpected diagnosis of OI. Explaining fetal MSC transplantation in a way that all parents can understand, clear expectation setting, psychological support and time for reflection during the decision-making process will be crucial to allow parents to make informed decisions about participation in the BOOSTB4 clinical trial.

Lin28b regulates age-dependent differences in murine platelet function

AbstractPlatelets are essential for hemostasis; however, several studies have identified age-dependent differences in platelet function. To better understand the origins of fetal platelet function, we have evaluated the contribution of the fetal-specific RNA binding protein Lin28b in the megakaryocyte/platelet lineage. Because activated fetal platelets have very low levels of P-selectin, we hypothesized that the expression of platelet P-selectin is part of a fetal-specific hematopoietic program conferred by Lin28b. Using the mouse as a model, we find that activated fetal platelets have low levels of P-selectin and do not readily associate with granulocytes in vitro and in vivo, relative to adult controls. Transcriptional analysis revealed high levels of Lin28b and Hmga2 in fetal, but not adult, megakaryocytes. Overexpression of LIN28B in adult mice significantly reduces the expression of P-selectin in platelets, and therefore identifies Lin28b as a negative regulator of P-selectin expression. Transplantation of fetal hematopoietic progenitors resulted in the production of platelets with low levels of P-selectin, suggesting that the developmental regulation of P-selectin is intrinsic and independent of differences between fetal and adult microenvironments. Last, we observe that the upregulation of P-selectin expression occurs postnatally, and the temporal kinetics of this upregulation are recapitulated by transplantation of fetal hematopoietic stem and progenitor cells into adult recipients. Taken together, these studies identify Lin28b as a new intrinsic regulator of fetal platelet function.

Transforming Growth Factor β1 in Patients with Type 2 Diabetes Mellitus After Fetal Pancreatic Stem Cell Transplant.

Our objective was to determine transforming growth factor β1 levels in patients with type 2 diabetes mellitus after fetal pancreatic stem cell transplant. We examined 10 patients (age range, 41-65 y) with type 2 diabetes mellitus, which we subsequently divided into 2 groups. Group 1 comprised 5 patients who received fetal pancreatic stem cell transplant (cells were 16-18 wk gestation) performed by intravenous infusion. Group 2 comprised 5 patients (control group) who were on hypoglycemic tablet therapy or insulin therapy. The quantity of fetal stem cells infused was 5 to 6 × 106. We analyzed transforming growth factor β1, C-peptide, and glycated hemoglobin levels in patients before and 3 months after fetal pancreatic stem cell transplant. In patients with type 2 diabetes mellitus, fetal pancreatic stem cell transplant led to a significant increase in transforming growth factor β1 levels, from 16 364.8 to 35 730.4 ng/mL (P = .008), with trend in decreased glycated hemoglobin levels, from 7.96% to 6.98% (P = .088) after 3 months. Transforming growth factor β1 levels increased significantly within 3 months after fetal pancreatic stem cell transplant in patients with type 2 diabetes mellitus.

Engineered T Regulatory Type 1 Cells for Clinical Application.

T regulatory cells, a specialized subset of T cells, are key players in modulating antigen (Ag)-specific immune responses in vivo. Inducible T regulatory type 1 (Tr1) cells are characterized by the co-expression of CD49b and lymphocyte-activation gene 3 (LAG-3) and the ability to secrete IL-10, TGF-β, and granzyme (Gz) B, in the absence of IL-4 and IL-17. The chief mechanisms by which Tr1 cells control immune responses are secretion of IL-10 and TGF-β and killing of myeloid cells via GzB. Tr1 cells, first described in peripheral blood of patients who developed tolerance after HLA-mismatched fetal liver hematopoietic stem cell transplantation, have been proven to modulate inflammatory and effector T cell responses in several immune-mediated diseases. The possibility to generate and expand Tr1 cells in vitro in an Ag-specific manner has led to their clinical use as cell therapy in patients. Clinical grade protocols to generate or to enrich and expand Tr1 cell medicinal products have been established. Proof-of-concept clinical trials with Tr1 cell products have demonstrated the safety and the feasibility of this approach and indicated some clinical benefit. In the present review, we provide an overview on protocols established to induce/expand Tr1 cells in vitro for clinical application and on results obtained in Tr1 cell-based clinical trials. Moreover, we will discuss a recently developed protocol to efficient convert human CD4+ T cells into a homogeneous population of Tr1-like cells by lentiviral vector-mediated IL-10 gene transfer.

Feasibility of combined treatment for type III spinal muscular atrophy: a pilot study

Feasibility of combined treatment for type III spinal muscular atrophy: a pilot study Nataliia Sych, 1 Mariya Klunnyk,1 Iryna Matiyashchuk,1 Mariya Demchuk,1 Olena Ivankova,1 Andriy Sinelnyk,1 Khrystyna Sorochynska,2 Marina Skalozub3 1Clinical Department, 2Stem Cells Bank, 3Laboratory and Biotechnology Department, Cell Therapy Center EmCell, Kyiv, Ukraine Objective: To find solutions and improve methods of therapy for patients suffering from type III spinal muscular atrophy (SMA-III) by way of a combination of conventional treatment (medicines, physiotherapy) and fetal stem cells (FSCs) transplantation using suspensions extracted from stem cells of fetal liver and brain of human embryos.Materials and methods: Our study included 7 children suffering from SMA-III, including 5 boys and 2 girls, aged from 3 to 12 years who were allocated into the main group (MG). SMA children in the MG were administered fetal stem cell preparations, mainly suspensions which contained fetal cells of human liver and fetal brain along with standard treatment (treatment by use of medicines if required and physiotherapy). The control group (CG) included 6 children – 3 boys and 3 girls aged from 3.5 to 13 years.Results: The authors proved effectiveness and safety of treatment using FSCs for patients with SMA-III. Improvement of forced vital capacity of lungs and forced expiratory volume per 1 second was characteristic for the patients of the MG, starting from the period of observation at 6 months after FSCs transplantation. In patients from the CG, such values revealed characteristic improvement at 12 months after FSCs treatment. Significant reductions of alanina aminotransferase, aspartate aminotransferase, creatine phosphokinase, and lactate dehydrogenase ranges have been recorded in the patients of the MG at 6 months after treatment with FSCs. Such values show a significant reduction at 12 months after treatment.Conclusion: FSCs use in complex treatment of patients with SMA results in stable disease compensation, improvement of laboratory results, and improved ranges of forced vital capacity and forced expiratory volume in 1 second. Keywords: fetal stem cells, forced expiratory volume per 1 second, forced vital capacity of the lungs, type III spinal muscular atrophy

Leptin Levels in Patients with Type 1 Diabetes Mellitus After Fetal Pancreatic Stem Cell Transplant.

Our objective was to determine leptin levels in patients with type 1 diabetes mellitus after fetal pancreatic stem cell transplant. Seven patients, aged 20 to 42 years, with type 1 diabetes mellitus received a fetal pancreatic stem cell transplant by intravenous infusion. The quantity of fetal stem cells infused was ≥ 5 × 10⁶, and the cells were of 12 to 14 weeks of gestation. We analyzed the levels of leptin, C-peptide, and antibodies to the islets of Langerhans before and 3 months after the transplant procedure. Fetal pancreatic stem cell transplant led to significant increases in leptin and C-peptide levels, from 4.63 ± 1.17 ng/mL and 0.09 ± 0.02 ng/mL to 7.71 ± 1.45 ng/mL (P < .05) and 0.22 ± 0.05 ng/mL (P < .005), respectively, without an increase in antibodies to the islets of Langerhans, which measured 0.64 ± 0.13 U/mL before transplant and 0.57 ± 0.18 U/mL 3 months later (P > .05). Leptin levels increase significantly within 3 months of fetal pancreatic stem cell transplant in patients with type 1 diabetes mellitus.

Complex Treatment of Multiple Sclerosis Patients by Use of Fetal Stem Cells

Objective: Refinement for all existing methods of treatment for the multiple sclerosis patients by means of combined method including conventional therapy and administration of fetal stem cells (FSCs)-suspensions containing stem cells derived from human fetal liver and brain. Materials and methods: 51 patients diagnosed with MS participated in the study including 27 men and 24 women aged 27 to 56 years. Average age range for men was 34.2 ± 1.2 years, for women it constituted 31.7 ± 1.3 years. 33 patients were allocated in the Main Group (MG) including 20 men (mean age 29.8 ± 2.2 years) and 13 women (average age 31.3 ± 2.1 years). The Control Group (CG) was composed of 18 patients diagnosed with MSincluding 10 men (mean age of 30.5 ± 1.2 years) and 8 women (average age 31.4 ± 1.4 years). Simultaneously, the scale of MMSE was applied for objective study of cognitive functions among our patients. State Trait Anxiety Inventory was effective for emotional-anxiety disturbances. In addition, we assessed depression in patients by means of Beck Depression Inventory. Results: Authors proved efficacy and safety of FSCs suspensions for MS patients. We emphasized a significant improvement of neurology deficit in the MG already over 6 months after fetal stem cells transplantation (FSCT), whereas the CG patients revealed such advantages over 12 months. Improvement of cognitive functions was characteristic for the MG starting from 6 months after FSCT. Anxiety and depression significantly decreased and these results were observed over 6 months after FSCT in the MG. In the CG, the same values which significantly decreased over 12 months after treatment and were recorded. Conclusion: FSCs use in complex treatment of patients with MS stabilizes disease compensation, improves cognitive functions as well as psycho-emotional state of the patients.

Fetal Stem Cells Use in Complex Treatment of Cancer of the Head of Pancreas

Abstract Objective: to identify efficacy of fetal stem cells use in treatment of the patients with cancer of caput pancreatis; to summarize all hematology advantages and positive effects on overall condition of the patients, improvement of their life quality. Material and methods: we studied 15 patients who had been suffering from cancer of the head of pancreas and were administered treatment by use of fetal stem cell (FSCs) suspensions at Cell Therapy Center EmCell. All such patients underwent general and clinical examination over 1 and 3 months after FSCs transplantation: we were using functional CT and ultrasonography (US) for assessment of organs of abdominal cavity. Results: FSCs treatment contributed to better life quality in patients of the MG who revealed improvement of asthenia syndrome components: reduced fatigability, less exhaustion and emotional instability; decrease in hyperesthesia and phenomena of vegetative dysfunction. In the patients of the MG leucocytes count was significantly reduced in comparison with indexes which were recorded prior to FSCs treatment. Such results might be an evidence of reduction in inflammation of biliary ducts, as well as decreased paracancerous inflammation in the patients under study. Conclusion: Combined use of FSCs and conventional therapy for the patients with caput pancreatis cancer is well-tolerated by all patients, leads to reduced intoxication contributing to improved tolerability of standard anti-cancer therapy and promotes better life quality in the cancer patients. Positive changes in cell-mediated immunity were recorded in the patients after treatment.

Use of Fetal Stem Cells for Slowing Down Aging of the Spine

The article outlines the principal processes of human locomotor apparatus attrition; it dwells upon importance of this problem for contemporary medicine development. Objective: analyzing the effects of fetal stem cells (FSCs) on the patients suffering from age-related vertebral column changes. Material and methods: The study group was composed of 16 male patients in age from 55 to 60 years, who were performed Thomayer’s test to evaluate overall mobility of the spine, whereas flexibility in the lumbar spine was determined with the help of Schober’s test. We also investigated effect of problems with spine on activities of daily living in the patients by means of the Oswestry questionnaire. All patients of the study group completed one course of treatment using FSCs. Results: Assessment of the results of treatment we made over 6 and 12 months following FSCs transplantation. All results received pertaining to evaluation of spine flexibility by Schober’s and Thomayer’s test prove positive influence of FSCs on mobility of vertebral column, resulting in elevation of physical activity of the patients who underwent stem cell treatment in accordance with the Oswestry questionnaire. Conclusion: FSCs therapy is the only maximally effective contemporary method directed at prevention of vertebral column senescence. This treatment mode allows maintaining physical properties of the cartilaginous tissue, preserving its strength and elasticity of intervertebral disks, contributes to strengthening of the pectoral muscle sling and, eventually, supports the human spine. Slowing down locomotor apparatus aging tends to enhance life quality of any individual.

Lentiviral Barcode Labeling and Transplantation of Fetal Liver Hematopoietic Stem and Progenitor Cells.

Cellular barcoding enables the dissection of clonal dynamics in heterogeneous cell populations through single cell lineage tracing. The labeling of hematopoietic stem and progenitor cells (HSPCs) with unique and heritable DNA barcodes, makes it possible to resolve donor cell heterogeneity in terms of differentiation potential and lineage bias at the single cell level, through subsequent transplantation and high-throughput sequencing. Furthermore, cellular barcoding allows for bona fide hematopoietic stem cells (HSCs) to be defined based on functional rather than immunophenotypic parameters. This protocol describes the work flow of lentiviral cellular barcoding, tracking 14.5 days post coitum (d.p.c.) fetal liver (FL) Lineage-Sca+cKit+ (LSK) HSPCs following long-term reconstitution (Figure 1) ( Kristiansen et al., 2016 ), but can be adapted to the cell type or time frame of choice. Figure 1.Summary of experimental workflow ( Naik et al., 2013 ).

Use of Fetal Stem Cells for Anti-Aging and Rejuvenation Therapy

Background: The main objective of our study was investigation of fetal stem cells (FSCs) effects on principal processes of human organism aging. Material and Methods: The main group (MG) was composed of 164 female patients and 165 male patients. Cardiovascular type of aging was remarkable for 66 patients, endocrine- 65, neuro-psychic- 70, metabolic- 50 and mixed type- was presented in 78 patients. For statistical analysis we studied the group of patients with mixed type of aging. All patients in the MG underwent treatment using FSCs. Preparations containing FSCs were individually selected for each patient depending on a definite type of aging; suspensions were administered via the parenteral route. Results: Patients experienced a syndrome of early post-infusion improvement which was presented as enhanced physical and emotional activity; better mood, improved sleep and appetite. Antiaging therapy using FSCs can promote a favorable effect on the lipids and carbohydrates metabolism; laboratory parameters of male health and overall physical state in patients; psycho-functional and emotional health were improved too. We recorded healthier skin in our patients; its dryness and scaliness (roughness) reduced; skin suppleness and elasticity increased and the patients also reported less number of wrinkles. Based on calculations we revealed that over 18 months after FSCs transplantation the aging rate among the patients became lower by 35.33%, whereas over 30 months it was reduced by 56.68%. Conclusion: Treatment using FSCs allows correlating internal factors of pre-term fading which result in lower external signs of aging among the patients; that, in bulk, contributes to overall revitalizing and rejuvenation along with inhibiting the rate of aging by way of promoting better life quality and life expectancy among the patients.

Counteracting bone fragility with human amniotic mesenchymal stem cells.

The impaired maturation of bone-forming osteoblasts results in reduced bone formation and subsequent bone weakening, which leads to a number of conditions such as osteogenesis imperfecta (OI). Transplantation of human fetal mesenchymal stem cells has been proposed as skeletal anabolic therapy to enhance bone formation, but the mechanisms underlying the contribution of the donor cells to bone health are poorly understood and require further elucidation. Here, we show that intraperitoneal injection of human amniotic mesenchymal stem cells (AFSCs) into a mouse model of OI (oim mice) reduced fracture susceptibility, increased bone strength, improved bone quality and micro-architecture, normalised bone remodelling and reduced TNFα and TGFβ sigalling. Donor cells engrafted into bones and differentiated into osteoblasts but importantly, also promoted endogenous osteogenesis and the maturation of resident osteoblasts. Together, these findings identify AFSC transplantation as a countermeasure to bone fragility. These data have wider implications for bone health and fracture reduction.

Modeling Human Leukemia Immunotherapy in Humanized Mice

The currently available human tumor xenograft models permit modeling of human cancers in vivo, but in immunocompromised hosts. Here we report a humanized mouse (hu-mouse) model made by transplantation of human fetal thymic tissue plus hematopoietic stem cells transduced with a leukemia-associated fusion gene MLL-AF9. In addition to normal human lymphohematopoietic reconstitution as seen in non-leukemic hu-mice, these hu-mice showed spontaneous development of B-cell acute lymphoblastic leukemia (B-ALL), which was transplantable to secondary recipients with an autologous human immune system. Using this model, we show that lymphopenia markedly improves the antitumor efficacy of recipient leukocyte infusion (RLI), a GVHD-free immunotherapy that induces antitumor responses in association with rejection of donor chimerism in mixed allogeneic chimeras. Our data demonstrate the potential of this leukemic hu-mouse model in modeling leukemia immunotherapy, and suggest that RLI may offer a safe treatment option for leukemia patients with severe lymphopenia.