Cord Blood Cell Transplantation Research Articles

Hal E. Broxmeyer PhD: Experimental hematologist and umbilical cord blood cell transplant pioneer (27 November, 1944–8 December, 2021)

Hal E. Broxmeyer PhD: Experimental hematologist and umbilical cord blood cell transplant pioneer (27 November, 1944–8 December, 2021)

Hal E. Broxmeyer PhD: Experimental haematologist and umbilical cord blood cell transplant pioneer (27 November, 1944–8 December, 2021)

Hal E. Broxmeyer PhD: Experimental haematologist and umbilical cord blood cell transplant pioneer (27 November, 1944–8 December, 2021)

Human Umbilical Cord Blood Therapy for Diabetes Mellitus : A Review

Stem cell therapy for patients with diabetes mellitus is receiving great attention among scientists and clinicians. Although bone marrow is considered one of the rich sources of stem cells, its limited availability of donors precludes its use for all the suitable patients. Human umbilical cord blood mononuclear cells or its-derived mesenchymal cells are being increasingly used as an alternative source of stem cells for cell-based therapy for malignant and nonmalignant diseases. Human umbilical cord blood cells have low potential for graft-versus-host disease and tumorigenicity. Also, no immunosuppression is required. Experimental evidence has shown that human umbilical cord blood -derived stem cells can differentiate into insulin-secreting β-cells. Transplantation of Human umbilical cord blood cells has been shown to improve blood glucose levels, and ameliorate kidney as well as neuropathic complications in diabetic animal models. Although the first use of autologous Human umbilical cord blood transfusion in type 1 diabetic children had a short-term beneficial effect in reducing the daily requirement of insulin dose and the maintenance of near normoglycemia, subsequent studies have failed to show this beneficial effect. In this review, we will provide both experimental and clinical evidence in favor and against the beneficial effect of human umbilical cord blood cells and cord blood-derived mesenchymal cells in the management of diabetes mellitus.

Potential Use of Mesenchymal Multipotent Cells for Hemopoietic Stem Cell Transplantation: Pro and Contra.

The potential of mesenchymal multipotent (stem) cells (MSC) to modify immune reactions and mediate hematopoiesis boosted great interest for their use in allogeneic hemopoietic stem cell transplantation. Because of MSC production of a wide range of cytokines and growth factors, these cells are included in the therapy of graft-versus-host disease (GVHD). A number of clinical studies have demonstrated safety and efficacy of MSC-based therapy in acute GVHD. Japan and some other countries approved biomedical cell products on the base of allogeneic bone marrow (BM) MSCs as medical agents for acute GVHD treatment. Besides, MSCs may form BM stroma and improve hematopoiesis. Simultaneous transplantation of hematopoietic stem cells and MSCs effectively improved engraftment and prevented GVHD in transplantation of umbilical cord blood and human leukocyte antigens-incompatible BM stem cells. The review presents the analysis of clinical studies of MSCs in allogeneic hematopoietic stem cell transplantation and discusses different approaches for improvement of MSC-based GVHD treatment and prophylaxis.

Clinical and functional aspects of cord blood cell transplantation in patients with distal lesion of lower limb arteries

To carry out a comparative analysis of the clinical condition of patients with distal lesions of the arterial bed using standard conservative therapy with cord blood cell transplantation and without it. The experimental group included patients with manifestations of chronic lower limb ischemia against the background of atherosclerosis, who underwent cord blood cell transplantation in combination with conservative therapy. The control group included patients with obliterating atherosclerosis and distal vascular lesions of the lower extremities, received a basic course of conservative therapy. To determine the quality of life before and after cord blood cell transplantation, we used a number of standardized questionnaires, which helped to determine the distance of intermittent claudication and make a subjective assessment of the personal well-being level of patients. To analyze the state of microcirculation in the ischemic limb, we used the laser Doppler flowmetry method. The following changes were observed after the cord blood cell transplantation: an improvement in the general state of patients, a decrease in the degree of ischemia according to Rutherford's classification, an increase in the distance and speed of painless walking during the first 3 months by 5-10%, and 1.3 times in 12 months compared with the control group. The improvement in the microcirculatory parameters of laser Doppler flowmetry was noted from the end of the first to the 12th month after transplantation, which indicated an improvement in microhemodynamics. The use of cord blood cell transplantation in order to stimulate angiogenesis allows one to obtain a long-term positive clinical effect, which manifests itself in the form of an increase in the distance and speed of painless walking, improved working capacity, and improved personal well-being of patients in the physical, psychological and socio-economic field, correlated with laser Doppler flowmetry data and expands the possibilities of successful treatment of patients with chronic ischemia of the lower extremities on the background of obliterating atherosclerosis.

Umbilical Cord Blood Cell Transplant Into Injured Spinal Cord With Lithium Carbonate or Placebo Followed by Locomotor Training

Umbilical Cord Blood Cell Transplant Into Injured Spinal Cord With Lithium Carbonate or Placebo Followed by Locomotor Training

Stimulation of rats fetuses growth by transplantation of rats bone marrow cells or human umbilical cord blood cells during gastrulation

Background & Aim In humans and animals with interstitial transplantation and hemochorial type of the placenta decidual cells (DC) differentiates in the uterus, and form the maternal part of the placenta. In the absence of DC development stops at the stage of merosome. Previously, we have shown that non-pregnant rats bone marrow cells transplantation (BMT) stimulates the development of DC in pseudo-pregnant rats. It is of interest to study the effect of pregnant rats bone-marrow cells on fetal development during transplantation in the early stages of pregnancy, as well as whether human umbilical cord blood cells have a similar effect. Methods, Results & Conclusion Bone marrow mononuclear cells (BMMC) of 4-13 days of pregnancy rats were administered intravenously to does of the same gestation period. The weight and morphology of the fetuses were evaluated on the 18th day of pregnancy. It was found that BMMC transplantation on 7-9 days of pregnancy significantly increased the weight of fetuses to 835 ± 15 mg compared to the weight of non-pregnant does (745 ± 11 mg) and the weight of does fetuses, which were administered BMMC of diestrus does (772 ± 9 m). Administration of BMMC on 11-12 days of pregnancy reduced fetal weight to 587 ± 5 mg. Also the umbilical cord blood mononuclear cells (UCBMC) was used in the study, which were administered subcutaneously in doses of 26 or 71 × 106 cells per 250 g of animal weight. Fetal weight on the 18th day of pregnancy was the maximum (856 ± 8 mg) with the administration of UCBMC on the 9th day of pregnancy. With the administration of UCBMC on day 11 of pregnancy fetal weight was reduced to 803 ± 19 mg. The dose reduction of the UCBMC to 26 × 106 resulted in the weight of the fetus on the 9th day of pregnancy decrease to 813 ± 17 mg. Thus, both rats BMMC and a human UCBMC stimulate 18th day of pregnancy fetus weight after administration to the female rats on the 7th, 8th and 9th days of pregnancy in the period of gastrulation. No morphological abnormalities were found in the fetuses. There is also no increase in post-implantation death, which indicates that the increase in fetal weight is not the result of compensatory growth. Similar results of transplantation of different types of cells indicate a general mechanism of fetal growth stimulation. It is possible that the result develops due to stimulation of decidual cell function but particular mechanisms of it are still need future researches.

Clinical management and viral genomic diversity analysis of a child's influenza A(H1N1)pdm09 infection in the context of a severe combined immunodeficiency

IntroductionA child with severe combined immunodeficiency (SCID) had an influenza A(H1N1)pdm09 infection with viral excretion longer than 6 months, during 2013–2014 influenza season, despite cord blood transplantation and antiviral treatments. MethodsConventional real-time RT-PCR methods were used to estimate viral load and to detect the presence of the common N1 neuraminidase (NA) H275Y substitution responsible for oseltamivir resistance. Next-generation sequencing (NGS) of influenza viruses was performed retrospectively to characterize viral quasispecies in specimens. ResultsThe patient was first treated with oral oseltamivir, leading to detection of low-levels of NA-H275Y substitution. Concomitant cord blood cell transplantation, intravenous administration of zanamivir and immunoglobulins led to an increase in white blood cells and influenza viral load decrease. A viral rebound occurred as soon as the antiviral treatment was discontinued. Eventually, influenza viral load was negated with immune reconstitution. NGS found influenza quasispecies harboring NA-E119A substitution (10.3%). Moreover, NGS showed that viral genomic diversity evolved under antiviral treatment and immune status. ConclusionsConventional virological techniques were sufficient for influenza infection follow-up but NGS performances allowed characterization of viral variants evolution in this specific case of prolonged influenza virus infection. New and efficient treatments against influenza in immunocompromised patients are needed.

Transplantation of cord blood cells as a method for the treatment of patients with distant artery of the lower limbs

Treatment of patients with distal lesions of the arteries of the lower extremities is a rather urgent problem. The aim is to compare the clinical status of patients with distal arterial disease before treatment and after using cord blood cells. We examined 16 patients with manifestations of chronic lower limb ischemia on the background of obliterating atherosclerosis. The patients were examined, the impossibility of performing reconstructive operations was determined, the cord blood cells were introduced into the ischemia zone. After transplantation, in most cases, positive clinical symptoms were observed. Patients noted improvement in their general condition, gradually decreased, and after 1-3 months and further there was no pain at rest, their working capacity improved, their family relationships were balanced, the degree of ischemia according to Pokrovsky-Fontein was reduced, the distance and the speed of painless walking increased in 1, 3 times after 12 months. Analyzing the value of LDF, an improvement in microcirculation processes was noted in patients with chronic limb ischemia 6–12 months after the transplantation of cord blood cells. The indices of the control radiopaque contrast angiography of the vessels of the lower extremities testified to a significant improvement in the distal blood flow, due to the developed collateral network. A clinical case of patient G., with a lesion of the lower limb arterial bed caused by obliterating atherosclerosis of the lower limb arteries, is presented. After transplantation of cord blood cells and stimulation of angiogenesis, a long-term positive clinical effect was obtained, which manifested itself in the form of an improvement in the general condition, a decrease in the degree of ischemia according to the Pokrovsky-Fontain classification, an increase in the distance and speed of painless walking, and an improvement in microcirculatory parameters. So, it has been clinically proven that the use of the cord blood cell transplantation method to patients who cannot perform direct reconstructive interventions expands the possibilities of successful treatment of patients with chronic lower limb ischemia against the background of obliterating atherosclerosis.

Morphological features of the regeneration of venous trophic ulcers with the use of cord blood stem cells in the experiment

Venous hypertension, which underlies the development of trophic disorders, initiates a complete cascade of pathological reactions at the molecular, cellular and tissue levels. Objectives – on our own model of the trophic ulcer, combined with venous hypertension, we investigated the processes occurring on the histological and immunohistochemical levels before and after stem cells of cord blood transplantation. Descriptive method for coloring histological sections, histochemical method for collagen fibers and fibrin, the immunohistochemical method for the detection of vimentin and the Villebrand factor and elements of morphometry were used. A comparative description of the morphological processes occurring in the treatment of the ulcerative defect of the soft tissues of the limbs on the background of chronic venous insufficiency after the transplantation and without the transplantation of stem cells of the cord blood was carried out. Experimental ulcer defects in the control of animals significantly decreased, some were completely healed. In the experimental group of animals ulcerative defects were healed in all cases. So, the application of stem cells of cord blood in a trophic ulcer of venous genesis leads to improved regeneration by accelerating the processes of differentiation of mesenchymal cells, activating the processes of angiogenesis, accelerating the maturation of the fibrous component of the stroma. The results of the study can serve as the basis for further study of the healing of ulcerative defect on the background of transplantation of cord blood cells and the development of new methods for complex treatment of patients with chronic venous ulcers.

CXCL12/CXCR4 Signaling Enhances Human PSC-Derived Hematopoietic ProgenitorFunction and Overcomes Early InVivo Transplantation Failure.

SummaryHuman pluripotent stem cells (hPSCs) generate hematopoietic progenitor cells (HPCs) but fail to engraft xenograft models used to detect adult/somatic hematopoietic stem cells (HSCs) from donors. Recent progress to derive hPSC-derived HSCs has relied on cell-autonomous forced expression of transcription factors; however, the relationship of bone marrow to transplanted cells remains unknown. Here, we quantified a failure of hPSC-HPCs to survive even 24 hr post transplantation. Across several hPSC-HPC differentiation methodologies, we identified the lack of CXCR4 expression and function. Ectopic CXCR4 conferred CXCL12 ligand-dependent signaling of hPSC-HPCs in biochemical assays and increased migration/chemotaxis, hematopoietic progenitor capacity, and survival and proliferation following in vivo transplantation. This was accompanied by a transcriptional shift of hPSC-HPCs toward somatic/adult sources, but this approach failed to produce long-term HSC xenograft reconstitution. Our results reveal that networks involving CXCR4 should be targeted to generate putative HSCs with in vivo function from hPSCs.

Comparison of Chronic Graft-Versus-Host Disease Severity and Functional Status after Cord Blood, Haploidentical Related and 1-Allele Mismatched Unrelated Donor Hematopoietic Cell Transplantation

Hematopoietic cell transplantation (HCT) can be accomplished with grafts from alternative donors for patients lacking an HLA-matched related or unrelated donor. The optimal choice of an alternative donor stem cell source remains an open question and is influenced by several factors including chronic graft-versus-host disease (cGVHD). Chronic GVHD is a heterogeneous syndrome with major morbidity and adverse effects on quality of life (QoL) among long-term allogeneic HCT survivors. The aim of this study was to analyze the incidence of cGVHD and manifestations associated with severe morbidity and poor functional outcomes among recipients with alternative HCT donors.Methods: This retrospective study included adults who received a first alternative donor HCT for any diagnosis between 2006 and 2015 in Seattle and subsequently developed cGVHD. The alternative grafts included unrelated 4-6/6-HLA-matched single or double cord blood units (UCB), related HLA-haploidentical bone marrow or mobilized blood stem cells with post-transplant cyclophosphamide (R-HAPLO), and mobilized blood cells from unrelated donors with 1-allele mismatching at an HLA-A, B, C or DR locus at any HLA-typing resolution (1-mMUD). Endpoints were cumulative incidence frequencies (CI) of cGVHD and the CI of manifestations associated with severe morbidity (i.e., grade 2 or 3 keratoconjunctivitis sicca, scleroderma-like skin features, grade 2 or 3 myofasciitis, bronchiolitis obliterans, or esophageal stricture requiring dilation) and the CI of functional outcomes (i.e., return to work/school after the diagnosis of cGVHD, discontinuation of systemic immunosuppressive therapy, and change in KPS). We also compared the 2014 NIH overall severity of cGVHD at initial diagnosis, the incidence of new systemic immunosuppression after first-line therapy for cGVHD, non-relapse mortality and overall survival after cGVHD diagnosis.Results: Of 396 alternative donor HCT recipients, 129 developed cGVHD and were included in this study. Chronic GVHD developed in 29 of 163 UCB recipients (3-year CI, 18%), 21 of 88 R-HAPLO recipients (24%) and 79 of 145 1-mMUD recipients (55%) HCT (Fig. 1A). The median follow-up times after onset of cGVHD were 48 (range 4-121) months for UCB, 60 (range <1-123) for R-HAPLO, and 46 (range 4-131) for 1-mMUD. Table 1 displays characteristics of cGVHD according to the alternative donor groups. The CI of any manifestation of severe morbidity at 3 years after a cGVHD diagnosis is shown in Fig. 1B and was significantly lower in UCB (14%) and R-HAPLO (23%) compared to the 1-mMUD group (58%) [hazard ratio (HR) 0.13 (95% Confidence Interval 0.1-0.4), p=<0.0001, and HR 0.31 (0.1-0.7), p=0.007, respectively]. Compared to the 1-mMUD group, a higher proportion of recipients of UCB (68% vs. 35%) returned to work/school at 3 years after cGVHD [HR 2.54 (1.1-5.7), p=0.02], and a similar trend was observed in R-HAPLO (62% vs. 35% [HR 2.38 (1.0-5.9), p=0.06)] (Fig. 1C). The CI of discontinued systemic immunosuppression at 3 years was significantly lower in the 1-mMUD (15%) compared to the UCB (45%) and R-HAPLO (50%) groups [HR 3.96 (1.9-8.4), p=0.0003, and HR 4.93 (2.2-11.1), p=0.0001, respectively], (Fig. 1D). We found trends suggesting improved annualized KPS change from cGVHD onset to 3.5 years in the UCB [+5 (range -12 to +44)] and R-HAPLO [+11 (range -14 to +64)] groups compared to the 1-mmUD group [0 (range -81 to +46)] (p=0.05 and p=0.06, respectively). The proportion of patients in each group requiring change in systemic therapy for control of cGVHD at 3 years after first line treatment was: 17% for UCB, 25% for R-HAPLO and 39% for 1-mMUD, and was significantly lower for UCB compared to the 1-mMUD group [HR 0.30 (0.1-0.8), p=0.01]. Non-relapse mortality and overall survival were similar among the 3 groups.Conclusions: Compared to 1-mMUD group, UCB and R-HAPLO HCT recipients were less likely to develop cGVHD. Among those with cGVHD, UCB and R-HAPLO HCT recipients were less likely to develop manifestations of severe morbidity, had less protracted cGVHD (a shorter duration of systemic treatment), and higher likelihood of resuming work or school, suggesting better QoL compared to 1-mMUD HCT recipients. Our results will help better counsel patients about alternative HCT donors. A randomized study (NCT01597778) comparing UCB with R-HAPLO HCT is underway to determine which of these donors may be associated with superior outcomes. [Display omitted] DisclosuresLee:Mallinckrodt: Honoraria; Amgen: Other: One-time advisory board member; Bristol-Myers-Squibb: Other: One-time advisory board member; Kadmon: Other: One-time advisory board member. Martin:Pfizer: Consultancy; Procter and Gamble: Equity Ownership; Incyte: Consultancy; Fresenius, Neovii: Research Funding. Cheng:Gilead Sciences, Inc.: Consultancy. Flowers:Pharmacyclics: Consultancy.

Granulocyte-colony stimulating factor and umbilical cord blood cell transplantation: Synergistic therapies for the treatment of traumatic brain injury.

Traumatic brain injury (TBI) is now characterized as a progressive, degenerative disease and continues to stand as a prevalent cause of death and disability. The pathophysiology of TBI is complex, with a variety of secondary cell death pathways occurring which may persist chronically following the initial cerebral insult. Current therapeutic options for TBI are minimal, with surgical intervention or rehabilitation therapy existing as the only viable treatments. Considering the success of stem-cell therapies in various other neurological diseases, their use has been proposed as a potential potent therapy for patients suffering TBI. Moreover, stem cells are highly amenable to adjunctive use with other therapies, providing an opportunity to overcome the inherent limitations of using a single therapeutic agent. Our research has verified this additive potential by demonstrating the efficacy of co-delivering human umbilical cord blood (hUCB) cells with granulocyte-colony stimulating factor (G-CSF) in a murine model of TBI, providing encouraging results which support the potential of this approach to treat patients suffering from TBI. These findings justify ongoing research toward uncovering the mechanisms which underlie the functional improvements exhibited by hUCB + G-CSF combination therapy, thereby facilitating its safe and effect transition into the clinic. This paper is a review article. Referred literature in this paper has been listed in the reference section. The datasets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors’ experiences.

Ex Vivo Expansion of Hematopoietic Stem and Progenitor Cells from Umbilical Cord Blood

Transplantation of umbilical cord blood cells is currently widely used in modern cell therapy. However, the limited number of hematopoietic stem and progenitor cells (HSPCs) and prolonged time of recovery after the transplantation are significant limitations in the use of cord blood. Ex vivo expansion with various cytokine combinations is one of the most common approaches for increasing the number of HSPCs from one cord blood unit. In addition, there are protocols that enable ex vivo amplification of cord blood cells based on native hematopoietic microenvironmental cues, including stromal components and the tissue-relevant oxygen level. The newest techniques for ex vivo expansion of HSPCs are based on data from the elucidation of the molecular mechanisms governing the hematopoietic niche function. Application of these methods has provided an improvement of several important clinical outcomes. Alternative methods of cord blood transplantation enhancement based on optimization of HPSC homing and engraftment in patient tissues have also been successful. The goal of the present review is to analyze recent methodological approaches to cord blood HSPC ex vivo amplification.

Возможности использования клеток кордовой крови в неврологии

This review represents the findings, reflecting the main achievements in the scope of cell based therapy of nervous diseases and therapeutic potential of cord blood cells in experimental and clinical neurology. The cord blood-derived cell populations are classified and the possibility of their application in therapy of neurological deficit is demonstrated. Different approaches to cord blood cell transplantation are considered, depending on administration way and cell concentration. Possible mechanisms of therapeutic effect of these cells, as well as their ability to migrate into the brain through the blood-brain barrier are discussed. Probl Cryobiol Cryomed 2016; 26(2):103-115.

Translating G-CSF as an Adjunct Therapy to Stem Cell Transplantation for Stroke.

Among recently investigated stroke therapies, stem cell treatment holds great promise by virtue of their putative ability to replace lost cells, promote endogenous neurogenesis,and produce behavioral and functional improvement through their "bystander effects." Translating stem cell in the clinic, however, presents a number of technical difficulties. A strategy suggested to enhance therapeutic utility of stem cells is combination therapy, i.e., co-transplantation of stem cells or adjunct treatment with pharmacological agents and substrates,which is assumed to produce more profound therapeutic benefits by circumventing limitations of individual treatments and facilitating complementary brain repair processes. We previously demonstrated enhanced functional effects of cotreatment with granulocyte-colony stimulating factor (GCSF)and human umbilical cord blood cell (hUCB) transplantation in animal models of traumatic brain injury (TBI). Here,we suggest that the aforementioned combination therapy may also produce synergistic effects in stroke. Accordingly, G-CSF treatment may reduce expression of pro-inflammatory cytokines and enhance neurogenesis rendering a receptive microenvironment for hUCB engraftment. Adjunct treatment of GCSF with hUCB may facilitate stemness maintenance and guide neural lineage commitment of hUCB cells. Moreover, regenerative mechanisms afforded by G-CSF-mobilized endogenous stem cells, secretion of growth factors by hUCB grafts and G-CSF-recruited endothelial progenitor cells(EPCs), as well as the potential graft–host integration that may promote synaptic circuitry re-establishment could altogether produce more pronounced functional improvement in stroked rats subjected to a combination G-CSF treatment and hUCB transplantation. Nevertheless, differences in pathology and repair processes underlying TBI and stroke deserve consideration when testing the effects of combinatorial G-CSF and hUCB cell transplantation for stroke treatment. Further studies are also required to determine the safety and efficacy of this intervention in both preclinical and clinical stroke studies.

Improving Quality and Potency Testing for Umbilical Cord Blood: A New Perspective.

This article critically reviews current methods to test and characterize umbilical cord blood (UCB) for hematopoietic stem cell transplantation. These tests include total nucleated cell (TNC) count, viability, viable CD34-positive content, and the colony-forming unit assay. It is assumed that the data obtained are sufficient to perform a UCB stem cell transplant without actually determining the quality and potency of the stem cells responsible for engraftment. This assumption has led not only to a high graft failure rate attributed to low or lack of potency, but also to noncompliance with present statutes that require UCB stem cells to be of high quality and, indeed, potency for a transplant to be successful. New evidence now calls into question the quality of the data, based on the UCB processed TNC fraction because using this impure fraction masks and significantly underestimates the functionality of the stem cells in both the segment and the unit. It is proposed that UCB units should be processed to the mononuclear cell fraction and that new cost-effective technology that measures the quality and potency of UCB stem cells be implemented to achieve better practices in UCB testing. These changes would provide the transplant physician with the assurance that the stem cells will perform as intended and would reduce risk and increase safety and efficacy for the patient. Current stem cell transplantation of umbilical cord blood cells requires testing that includes four basic parameters that do not determine whether the stem cells are of high quality, as required by the Stem Cell Therapeutic and Research Act of 2005. No cord blood units collected or transplanted so far have been tested for stem cell quality or potency. New scientific evidence calls into question cord blood processing and testing practices required by regulatory agencies and standards organizations. A new perspective is described that includes stem cell quality and potency testing that could reduce graft failure rates.

Changes of intracardiac hemodynamics in patients with decreased myocardial contractility at transplantation of cord blood stem cells

Experiments on animals have shown an effectiveness of cord blood stem cells (SCs) in restoration of myocardial contractility. But there is not enough information about the use of this SCs type at heart lesion in people. Therefore, the aim of this study was to analyze the effect of cord blood SCs transplantation on impaired myocardial contractility of patients with chronic heart failure.Materials and methods. According to the data echocardiography we analyzed the changes of intracardiac hemodynamics in patients with decreased myocardial contractility, who underwent intravenous transplantation of cord blood stem cells in case of ineffective traditional conservative therapy schemes of heart failure (HF).Results. Left ventricular ejection fraction before cord blood stem cells transplantation was 22.0 ± 5.0 %, 1 month after SC transplantation – 22.3 ± 6.5%, and in 3 months – 28.5 ± 7.8 % (p &lt; 0.05). The average stroke index increased from 21.3 ± 3.5 ml/m2 before transplantation up to 29.0 ± 8.5 ml/m2 3 months after transplantation SC (p &lt; 0.05). Statistically significant changes of diastolic function parameters (index e’, E/A, E/e’) and venous stasis have not been established. Before transplantation local cell contractility index (LCI) of basal and middle segments was 2.43 points; 1 month after transplantation LCI decreased to 2.38, and after 3 months – up to 2.18 points (p &lt;0.05).Conclusion. In a short term (1-3 months) after transplantation of cord blood cells there was demonstrated a partial restoration of parameters that characterize left ventricular systolic function, and a significant improvement of impaired heart rate mechanics. No negative effects, complications and side effects have been recorded in short periods of observation after transplantation of cord blood cells.

Symptomatic improvement, increased life-span and sustained cell homing in amyotrophic lateral sclerosis after transplantation of human umbilical cord blood cells genetically modified with adeno-viral vectors expressing a neuro-protective factor and a neural cell adhesion molecule.

Amyotrophic lateral sclerosis (ALS) is an incurable, chronic, fatal neuro-degenerative disease characterized by progressive loss of moto-neurons and paralysis of skeletal muscles. Reactivating dysfunctional areas is under earnest investigation utilizing various approaches. Here we present an innovative gene-cell construct aimed at reviving inert structure and function. Human umbilical cord blood cells (hUCBCs) transduced with adeno-viral vectors encoding human VEGF, GDNF and/or NCAM genes were transplanted into transgenic ALS mice models. Significant improvement in behavioral performance (open-field and grip-strength tests), as well as increased life-span was observed in rodents treated with NCAM-VEGF or NCAM-GDNF co-transfected cells. Active trans-gene expression was found in the spinal cord of ALS mice 10 weeks after delivering genetically modified hUCBCs, and cells were detectable even 5 months following transplantation. Our gene-cell therapy model yielded prominent symptomatic control and prolonged life-time in ALS. Incredible survivability of xeno-transpanted cells was also observed without any immune-suppression. These results suggest that engineered hUCBCs may offer effective gene-cell therapy in ALS.

G-CSF as an adjunctive therapy with umbilical cord blood cell transplantation for traumatic brain injury.

Traumatic brain injury (TBI), a major contributor to deaths and permanent disability worldwide, has been recently described as a progressive cell death process rather than an acute event. TBI pathophysiology is complicated and can be distinguished by the initial primary injury and the subsequent secondary injury that ensues days after the trauma. Therapeutic opportunities for TBI remain very limited with patients subjected to surgery or rehabilitation therapy. The efficacy of stem cell-based interventions, as well as neuroprotective agents in other neurological disorders of which pathologies overlap with TBI, indicates their potential as alternative TBI treatments. Furthermore, their therapeutic limitations may be augmented when combination therapy is pursued instead of using a single agent. Indeed, we demonstrated remarkable combined efficacy of human umbilical cord blood (hUCB) cell therapy and granulocyte-colony-stimulating factor (G-CSF) treatment in TBI models, providing essential evidence for the translation of this approach to treat TBI. Further studies are warranted to determine the mechanisms underlying therapeutic benefits exerted by hUCB + G-CSF in order to enhance its safety and efficacy in the clinic.