Autologous Stem Cell Research Articles

Autologous hematopoietic stem cell transplantation in the treatment of systemic sclerosis. Part 2. Safety and complications

Autologous hematopoietic stem cell transplantation (auto-HSCT) is presently the only disease-modifying strategy for the treatment of systemic sclerosis (SSs) that has Level A evidence, the effectiveness of which has been proven in three controlled clinical trials: ASSIST, ASTIS, and SCOT. Despite the positive results obtained with the use of this treatment option, the issues related to its tolerability and safety remain unresolved. The complications caused by obvious immunosuppression and higher frequency of infections are the main causes of death after autoHSCT for autoimmune diseases and occur mainly in the first month after treatment. Overall, the studies performed confirm the overall assessment of auto-HSCT as an effective and relatively safe treatment for severe SSs.

Pilot Study of Mesenchymal Stem Cells in Progressive Multiple Sclerosis

Autologous mesenchymal stem cells (MSCs) are hypothesized to have immunomodulatory and neurotrophic effects. In the present study, 48 patients with

Аутологичная трансплантация гемопоэтических стволовых клеток при ВИЧ-ассоциированной плазмобластной лимфоме: клинический случай

Plasmablastic lymphoma (PBL) is a disease that was originally described in 1997 as a distinct subtype of diffuse large B-cell lymphoma (DLBCL), which is more common in patients with HIV infection. It is characterized by extranodal lesions, the most common of which are the oral cavity, digestive tract, and skin3. No generally accepted chemotherapy protocol for the treatment of HIV-associated PBL has been developed. Early consolidation through autologous hematopoietic stem cell transplantation (auto-HSCT) may be a treatment option for advanced patients with concurrent use of highly active antiretroviral therapy (HAART). Disease history. Patient B., 44 years old, with HIV-associated PBL-IV-stage according to AnnArbor with lesions of the alveolar process of the upper jaw, lymph nodes of the neck on the left, bronchopulmonary lymph nodes, and the lower lobe of the right lung, who after 6 courses of chemotherapy according to the standard CHOP regimen, autotransplantation of hematopoietic stem cells was performed in the first remission. Conclusion. Our clinical experience correlates with the few studies on this issue. The patient received stem cell-supported high-dose chemotherapy (HDCT) and his life expectancy is 36 months. Keywords: plasmablastic lymphoma, HIV-associated lymphomas, autologous hematopoietic stem cell transplantation.

Characteristics of respiratory virus infections in autologous hematopoietic stem cell transplantation patients, a prospective study, Bern, Switzerland, 2015–2017

Background The epidemiology of respiratory virus infections (RVI) in patients undergoing autologous haematopoietic stem cell transplantation (auto-SCT) is not well described. Methods Our goal was to describe the epidemiology of respiratory virus infections (RVI) in patients undergoing autologous haematopoietic stem cell transplantation (auto-SCT) in a single tertiary centre observation study during two respiratory virus seasons (2015–2017). All symptomatic auto-SCT patients were tested for RVI by nasopharyngeal swab. Results 156 transplantation episodes were included, 69% were male and, the median age was 57 years. We detected 19 RVIs in 156 transplantation episodes (12%). The median time to RVI after hospitalization was 13 days [IQR 7–13] and 15/19 (79%) had a possible nosocomial origin (occurrence ≥ 5 days after admission). The nosocomial infections included 5/15 (33%) ‘severe’ RVIs (3 influenza viruses, 1 parainfluenza virus, and 1 adenovirus) as well as 10/15 (66%) non-severe virus infections (including human rhinovirus and human coronavirus). Conclusion In approximately 10% of auto-SCT transplantation episodes, an RVI with likely nosocomial origin was detected and included ‘severe viruses’ such as influenza. Our study suggests that infection prevention measures in auto-SCT patients can be improved. Abbreviations AdV: adenovirus; ALL: acute lymphatic leukaemia; AML: acute myeloid leukaemia; auto-SCT: autologous haematopoietic stem cell transplantation; hCoV: human coronavirus; HD: Hodgkin’s disease; hMPV: human metapneumovirus; HRV: human rhinovirus; HSCT: allogeneic haematopoietic stem cell transplantation; IQR: interquartile range; GCT: germ cell tumour; MM: multiple myeloma; NHL: non-Hodgkin lymphoma; PIV: parainfluenza virus; RSV: respiratory syncytial virus

The Combination of Jiedu Xiaoluo Decoction with Autologous Peripheral Blood Stem Cell Transplantation (APBSCT) Accelerates Disease Remission of Non-Hodgkin Lymphoma

Objective This study aimed to explore the therapeutic effects of autologous peripheral blood stem cell transplantation (APBSCT) with Jiedu Xiaoluo decoction (JDX) on non-Hodgkin lymphoma (NHL). Method B lymphoma cells A20 were used to establish nude mice-transplanted tumor model. The peripheral blood of mice was analyzed by automatic blood cell counter. Inflammatory cytokines in tumor tissues were measured by ELISA, real-time qRT-PCR, and western blotting assays. Immunohistochemical staining was employed to evaluate tumor cell growth and apoptosis. CCK8 and Transwell assays were used to detect cell viability, migration, and invasion. Cell apoptosis in vitro was evaluated with flow cytometry. Result In the in vitro co-culture system of A20 cells and hemopoietic stem cells (HSC), JDX notably inhibited the proliferation, migration, and invasion and promoted apoptosis of A20 cells compared to HSC treatment alone. In animal tumor xenografts of NHL, the combination of APBSCT with JDX significantly promoted hematopoietic reconstitution, inhibited tumorigenesis of A20 cell, promoted the inflammatory microenvironment remission, inhibited cell proliferation, and promoted apoptosis compared to APBSCT alone. Conclusion The combination of APBSCT with JDX might be an effective strategy to treat NHL through inhibiting tumorigenesis and reconstructing hematopoietic and immune microenvironment. Our finding provided a novel insight into the clinical application of Traditional Chinese Medicine (TCM) against NHL.

Long-Term Cryopreservation Does Not Affect Quality of Peripheral Blood Stem Cell Grafts: A Comparative Study of Native, Short-Term and Long-Term Cryopreserved Haematopoietic Stem Cells

Cryopreserved haematopoietic progenitor cells are used to restore autologous haematopoiesis after high dose chemotherapy. Although the cells are routinely stored for a long period, concerns remain about the maximum storage time and the possible negative effect of storage on their potency. We evaluated the effect of cryopreservation on the quality of peripheral stem cell grafts stored for a short (3 months) and a long (10 years) period and we compared it to native products.The viability of CD34+ cells remained unaffected during storage, the apoptotic cells were represented up to 10% and did not differ between groups. The clonogenic activity measured by ATP production has decreased with the length of storage (ATP/cell 1.28 nM in native vs. 0.63 in long term stored products, P < 0.05). Only borderline changes without statistical significance were detected when examining mitochondrial and aldehyde dehydrogenase metabolic activity and intracellular pH, showing their good preservation during cell storage. Our experience demonstrates that cryostorage has no major negative effect on stem cell quality and potency, and therefore autologous stem cells can be stored safely for an extended period of at least 10 years. On the other hand, long term storage for 10 years and longer may lead to mild reduction of clonogenic capacity. When a sufficient dose of stem cells is infused, these changes will not have a clinical impact. However, in products stored beyond 10 years, especially when a low number of CD34+ cells is available, the quality of stem cell graft should be verified before infusion using the appropriate potency assays.

The Evaluation of Melatonin Effects on Mobilization and Engraftment in Autologous Hematopoietic Stem Cell Transplant Recipients; A Randomized, Double-blind and Placebo-controlled Trial.

Mobilization and engraftment of Hematopoietic Stem Cells (HSCs) are challenging issues in Autologous HSC transplantation (AHSCT) so several attempts such as colony-stimulating factors (CSF) and plerixafor have been used for enhancement of HSCs mobilization and engraftment. In this randomized, double-blind and placebo-controlled study, we evaluated the melatonin’s efficacy and safety, as endogenous CSF inducer, co-administered with Filgrastim in mobilizing and engraftment of HSC. AHSCT patients were randomized to receive either Melatonin or placebo plus filgrastim. Of Fifty-one patients, 26 patients received the melatonin (In mobilization phase 3 mg sublingual twice daily, then 9 mg single dose 30 min before apheresis session and then 3 mg twice daily from +1 until engraftment) and 25 patients received the placebo. The mean number of CD34 cells/kg × 106 in the melatonin group was 6.54 versus 4.22 in the placebo group (p = 0.025). The mean day to neutrophil engraftment in the melatonin group was 11.69 ± 2.093, whereas 12.68 ± 2.42 days in the placebo group (p = 0.021). In this study, the second apheresis session requirement, the use of plerixafor and hospital stay duration, were comparable between the two groups. Considering the result of the study, it could be suggested that melatonin plus Filgrastim can be effectively used in AHSCT patients to enhance the number of peripheral CD34 cells/kg × 106 and decrease the day number of neutrophil engraftment.

Efficacy and cost of G-CSF derivatives for prophylaxis of febrile neutropenia in lymphoma and multiple myeloma patients underwent autologous hematopoietic stem cell transplantation

ABSTRACT Objectives To compare the efficacies and costs between pegfilgrastim and filgrastim prophylaxis for FN post-ASCT for lymphoma and multiple myeloma patients. Methods 43 patients who received pegfilgrastim (6 mg) were compared to a retrospective cohort of 129 patients that had received filgrastim post-ASCT. Hematopoietic recovery time, FN incidence and treatment costs were assessed and compared. Results The mean time to absolute neutrophil count engraftment was 8.72 ± 2.38 days for the prospective pegfilgrastim group and 9.87 ± 3.13 days for the retrospective filgrastim group (P = 0.027). The incidence of FN was 18.60% and 50.39% in prospective pegfilgrastim and retrospective filgrastim groups, respectively (P = 0.000). The mean cost of filgrastim was $617.22 ± 37.87, compared with $525.78 for pegfilgrastim (P = 0.032). Discussion Convenience, effectiveness, and safety of prophylaxis for FN in the prospective pegfilgrastim group were significantly improved compared to the retrospective filgrastim group in ASCT patients. Conclusion Pegfilgrastim prophylaxis was more effective and convenient than filgrastim for FN prophylaxis in patients post-ASCT, especially for MM patients.

Tracking of autologous mesenchymal stem cells after intravenous and intrathecal transplantation in patients with spinal cord injury

Tracking of autologous mesenchymal stem cells after intravenous and intrathecal transplantation in patients with spinal cord injury

Quality of life and changes in the social dimension of hematopoietic stem cell transplants recipients.

to assess/correlate health-related quality of life with the social dimension of hematopoietic, autologous and allogeneic stem cell transplant patients in the three years post-transplant. longitudinal, observational study with 55 patients, in a reference hospital in Latin America, from September 2013 to February 2019, using the Quality of Life Questionnaire-Core and Functional Assessment Cancer Therapy Bone Marrow Transplantation. A total of 71% underwent allogeneic transplantation. The social dimension had low averages since the baseline stage (55, 21) and low scores (56) for quality of life in pancytopenia. There was a significant positive correlation between social dimension, quality of life in pancytopenia (p<0.01) and follow-up after hospital discharge (p<0.00). There is a significant difference (p<0.00) throughout the stages, however, not in terms of the type of transplant (p>0.36/0.86). patients with better assessments in the social dimension have a better quality of life. Interventions focusing on the multidimensionality of the quality of life construct are necessary.

An alternative in vivo model to evaluate pluripotency of patient-specific iPSCs.

The generation of autologous human induced pluripotent stem cells (hiPSCs) from a patient’s somatic cells and the sub­sequent differentiation of these cells into desired cell types offer innovative treatment options for tissue regeneration. The hiPSCs obtained are usually implanted in immunodeficient mice, and teratoma formation is analyzed after 4 to 6 weeks to assess the cells’ pluripotency. In this study, an alternative in vivo model based on chicken egg chorioallantoic membrane (CAM) was established to analyze the pluripotency of newly created hiPSCs. 0.5, 1, 2, 4 x 106 hiPSCs gen­erated from urine-derived renal epithelial cells were seeded on CAM and incubated for 9 days. Teratoma formation was detected in 70% of eggs inoculated with 2 x 106 hiPSCs and in 100% of eggs inoculated with 4 x 106 hiPSCs. All teratomas exhibited vascular structures. The robustness of the CAM model was confirmed using two additional hiPSC lines derived from human fibroblasts (NuFFs) or jaw periosteal cells. The presence of all three germ layers within the teratomas was successfully verified by histochemical and immunofluorescence staining and gene expression analysis of germ layer-specific markers. Urine-derived renal epithelial cells were used as negative control and showed no teratoma formation. The CAM-based in vivo model provides an optimal in vivo test environment for the pluripotency evaluation of newly generated hiPSC lines. This simple, fast, inexpensive and reproducible method reduces the suffering of animals and thus implements the principles of the 3Rs (replacement, reduction, and refinement).

Infections in hematopoietic stem cell transplant patients admitted to Hematology intensive care unit: a single-center study

ABSTRACT Objective The aim of this study was to investigate the data of HSCT patients who were admitted to our Hematology ICU due to infections or infectious complications. Materials and Methods HSCT patients who were admitted to our Hematology ICU between 01 January 2014 and 01 September 2017 were analyzed retrospectively. Results 62 HSCT patients were included in this study. The median age was 55.5 years and 58% of the patients were allogeneic HSCT patients. Major underlying hematologic disorders were multiple myeloma (29%) and lymphoma (27.4%). The most common reasons for ICU admission were sepsis/septic shock (61.3%) and acute respiratory failure (54.8%). Overall ICU mortality rate was 45.2%. However, a lot of factors were related with ICU mortality of HSCT patients in univariate analysis, only APACHE II score was found to be an independent risk factor for ICU mortality. While there was infection in 58 patients at ICU admission, new infections developed in 38 patients during ICU stay. The most common new infection was pneumonia/VAP, while the most frequently isolated bacteria were Acinetobacter baumannii. Length of ICU stay, sepsis/septic shock as a reason for ICU admission and the presence of urinary catheter at ICU admission were determined factors for ICU-acquired infections. There was no difference between autologous and allogeneic stem cell transplant patients in terms of ICU morbidities and mortality. However, pneumonia/VAP developed in the ICU was higher in autologous HSCT patients, while bloodstream/catheter-related bloodstream infection was higher in allogeneic HSCT patients. Conclusion It was concluded that early or late post-HSCT infections and related complications (sepsis, organ failure, etc.) constituted a major part of the reasons for ICU admission, ICU mortality and ICU morbidities.

Complete remission of scleredema adultorum of Buschke associated with multiple myeloma after bortezomib-based treatment and autologous peripheral blood stem cell transplantation

Complete remission of scleredema adultorum of Buschke associated with multiple myeloma after bortezomib-based treatment and autologous peripheral blood stem cell transplantation

Вплив мезенхімальних стовбурових клітин та плазми крові, збагаченої тромбоцитами, на перебіг хронічного ламініту у коня: клінічний випадок

Laminitis or rheumatic inflammation of the hooves is inflammation of the hoof lamina, in which the connection between the coffin bone and the horny shoe is disrupted as a result of the destruction of the connection between the leaves of the horny wall with the leaves of the base of the hoof skin. The pathogenesis of this disease is quite complex and contradictory. Some authors associate it with the accumulation of biogenic amines in the hoof tissues, while others point to the violation of lamellar microcirculation and the effect of tissue metalloproteinases on the leaves of the horny wall and the base of the hoof skin. Treating horses with laminitis is not an easy task, due to the complex pathogenesis of the disease. Thus, the search for modern treatments of horses with laminitis is an urgent and timely task. The aim of our study was to investigate the effect of adipose-derived mesenchymal stem cells and platelet-rich plasma on the course of chronic laminitis in horses. The object of the study was a castrated stallion of a Ukrainian riding breed, 8 years old, with a clinical manifestation of chronic laminitis with detachment of the hoof wall along the border line on the left forelimb. Materials and methods. Autologous mesenchymal stem cells were obtained from adipose tissue. A culture of mesenchymal stem cells of adipose tissue in the amount of 12 million cells was injected into the palmar medial digital artery of the injured limb. The introduction was repeated three times, while the cells were suspended in 3 cm3 of phosphate-buffered saline. The third injection of cells was performed in combination with autologous platelet-rich plasma. Results: Active recovery of the hoof wall was observed on the injured forelimb. Coronary fistulas and damage of the hoof joint capsule were healed. The shape of the hoof wall and sole began to normalize. The pulsation of the arteries of the toes has become less pronounced. No corona edema was observed in the area. Conclusion. Under the influence of transplanted mesenchymal stem cells and platelet-rich blood plasma, tissue structures of the injured hoof had restored as the clinical and functional state of the injured limb; at the same time, the x-ray picture of the hoof worsens, which is accompanied by irreversible processes in the hoof tissues and its deformation.

伴PML隐匿断裂点t(15;17)(q22;q21)阴性急性早幼粒细胞白血病一例报告并文献复习

伴PML隐匿断裂点t(15;17)(q22;q21)阴性急性早幼粒细胞白血病一例报告并文献复习

Assessment of quality of life three years from hematopoietic stem cell transplant.

To assess the domains of quality of life related to hematologic cancer patient health in the first three years from autologous and allogeneic hematopoietic stem cell transplantation. A prospective cohort from September 2013 to February 2019 at a reference service in Latin America with 55 patients. The instruments Quality of Life Questionnaire Core C30 and Functional Assessment Cancer Therapy - Bone Marrow Transplantation were used. For data analysis, Generalized Linear Mixed Model was used. The domains global and overall quality of life presented the lowest scores in the pancytopenia phase: 59.3 and 91.4 in autologous, 55.3 and 90.3 in allogeneic. The mixed method analysis has shown that there was a significant change in scores between the phases throughout the treatment (p< 0.05). Health-related quality of life presented significant changes in the domains between the phases throughout time. Understanding these results enables nursing interventions directed at the domains which were damaged during treatment.

Therapeutic Effect of Intravenously Administered Autologous Adipocyte-Derived Stem Cells on Chronic Stage Stroke Patients

Therapeutic Effect of Intravenously Administered Autologous Adipocyte-Derived Stem Cells on Chronic Stage Stroke Patients

Autologous cell using for the restoration of functional defects in patients with ischemic cerebrovascular accident

Stroke is a global medical and socio-economic problem and a great demand for alternative therapies, the leading one being stem cell (SC) therapy. Pathogenetic processes in ischemic stroke (II) trigger the mechanisms of necrotic and apoptotic death of neurons with the formation of the central infarct zone («core of ischemia») and the ischemic «penumbra» zone; the severity and reversibility of the injury directly depends on the duration of ischemia. In parallel with pathogenetic processes, endogenous neurogenesis occurs – the proliferation of neurogenic stem and progenitor cells (NSC/NPC) and their migration into the ischemic focus; however, most NSCs and newly formed neurons undergo apoptosis and recovery of lost functions does not occur. Significant efforts are being made to find ways to control neurogenesis, in particular through the transplantation of exogenous SCs. The main factors preventing the use of SCs in humans are moral, ethical, religious and legal aspects related to the source and method of obtaining cells, as well as possible immunocompromised complications due to incompatibility of donor cells with the recipient of the main histocompatibility complex antigens. The safest is the use of autologous SCs (the patient’s own cells), as it does not require the use of immunosuppressive protocols. Due to the relative safety and ease of production, the most common are multipotent mesenchymal stem cells (MSCs), namely MSCs of the bone marrow (BM). Numerous preclinical studies in experimental animals with modeled II, as well as clinical trials conducted over the past 15 years, have shown the safety and feasibility of transplantation of autologous MSCs in patients with severe neurological deficits after II. Two different approaches to the use of MSCs are discussed: neuroprotection in the acute phase and neurorestoration in the chronic phase II. Proposals are currently being developed for phase II/III clinical trials in acute and chronic stroke using BM MSCs, the results of which will form the basis for certified standardized II treatment protocols.

Effectiveness of Autologous Schwann Cell and Bone Marrow-Derived Mesenchymal Stem Cell Transplantation for Individuals With Spinal Cord Injury in Promoting Sensory Recovery

Background: In recent decades, improvement in sensory and motor function after spinal cord injury(SCI) is a major treatment goal. Stem cell therapy has become a promising treatment strategy in theregeneration of central nervous system injuries.Methods: We assessed the effectiveness of autologous Schwann cell (SC) and bone marrow-derivedmesenchymal stem cell (MSC) for individuals with SCI in promoting sensory recovery. Five patientswith a mean ± SD age of 38.80 ± 5.84 years were enrolled in the study. The follow-up course was12 months.Results: We found sensory changes in two patients assessed by the American Spinal InjuryAssociation’s (ASIA’s) impairment scale. Systemic complications were not observed during thecourse of the study.Conclusion: There were no adverse finding after cell transplantation. Also we observed improvementin sensory score in two patients. It seems that the use of this combination of cell therapy may beeffective; but large group studies with control group are required to clarify the effect of either cells.

The effectiveness of autologous mesenchymal stem cells in the treatment of liver cirrhosis and the method of their visualization in the patient’s body

Abstract. The effectiveness of the influence of autologous mesenchymal stem cells on the function of liver tissue in liver cirrhosis of alimentary etiology is considered, as well as the possibility of visualization of the introduced cell structures with subsequent cytological confirmation. To be able to track autologous mesenchymal stem cells introduced in the patients body, they were labeled with iron oxide nanoparticles. Visualization of the introduced cell structures was performed using magnetic resonance imaging and ultrasound examination of the liver. 6 months after the cell therapy, clinical and biochemical blood tests, lidocaine test results, elastography indicators were evaluated, and the dynamics of hepatic encephalopathy was evaluated. The effectiveness of using autologous mesenchymal stem cells was evidenced by the improvement of the above indicators. Also, 6 months after treatment, a liver tissue biopsy was performed from the sites of fixation of previously introduced cell structures. Histological examination revealed the largest number of labeled cells in the liver micro-nodes, as well as at the borders of micro-nodes and fibrous septa. The use of cell therapy in a patient suffering from liver cirrhosis of alimentary etiology helped to improve the indicators of laboratory and instrumental research methods. No complications were detected during the procedure.