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

2018 ◽  
Vol 22 (3) ◽  
pp. 412-416
Author(s):  
D. B. Dombrovskyi ◽  
Yu. V. Olinyk ◽  
I. S. Davydenko
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Soft Tissues ◽  
Cord Blood Transplantation ◽  
Venous Hypertension ◽  
Immunohistochemical Method ◽  
Experimental Ulcer ◽  
Blood Transplantation ◽  
Before And After ◽  
Cord Blood Cells

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.

FEATURES

2012 ◽  
Vol 16 (07) ◽  
pp. 32-44
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Cancer Patients ◽  
Umbilical Cord ◽  
Blood Cells ◽  
Cord Blood Transplantation ◽  
Umbilical Cord Blood Transplantation ◽  
Blood Transplantation ◽  
Cord Blood Banking ◽  
Cord Blood Cells

Growing Cord Blood Cells for Cancer Patients. Umbilical Cord Blood Transplantation in Adults - The Debate between One vs. Two Units. Stem Cells in Umbilical Cord. Cord Blood Banking - To Go Public or Stay Private.

Cord blood transplantation provides better reconstitution of hematopoietic reservoir compared with bone marrow transplantation

Blood ◽  
2003 ◽  
Vol 102 (3) ◽  
pp. 1138-1141 ◽  
Author(s):  
Francesco Frassoni ◽  
Marina Podestà ◽  
Rita Maccario ◽  
Giovanna Giorgiani ◽  
Gabriele Rossi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cord Blood ◽  
Mononuclear Cells ◽  
Cord Blood Transplantation ◽  
Hematopoietic Progenitor Cell ◽  
Transplant Recipients ◽  
Platelet Recovery ◽  
Blood Transplantation

Abstract Delayed hematopoietic recovery is the main factor precluding a wider use of cord blood (CB) transplants. We hypothesized that this delayed engraftment might not be related to an insufficient number of stem cells in the graft, but to an intrinsic difficulty of these cells to undergo differentiation. To test our hypothesis, 2 groups of children were compared; 12 received a CB transplant and 12 an adult bone marrow (BM) transplant. We studied neutrophil and platelet recovery and, at a median time of approximately 1 year after transplantation, the frequency of colony-forming cells (CFCs) and long-term culture initiating cells (LTC-ICs) in the BM of the 2 groups. Recipients of BM transplants received 1-log more cells and had significantly faster neutrophil and platelet recovery. Conversely, the frequency of committed and early progenitors was significantly higher in the BM of children given CB cells compared with BM transplant recipients (median count of CFC/2 × 104 BM mononuclear cells, 20 versus 11, P = .007; median count of LTC-IC/106 BM mononuclear cells, 8.2 versus 0.2 P = .001). CB, but not adult BM stem cells, can better restore the host hematopoietic progenitor cell reservoir; the delayed engraftment after CB transplantation may reflect the difficulty of CB progenitors to reprogram themselves toward differentiation.

Economic Analysis of Reduced-Intensity Cord Blood Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5189-5189
Author(s):  
Koichiro Yuji ◽  
Shigesaburo Miyakoshi ◽  
Tomohiro Myojo ◽  
Yuji Miura ◽  
Daisuke Kato ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Stem Cells ◽  
Economic Analysis ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Hospital Death ◽  
Blood Transplantation ◽  
The Mean ◽  
The Cost ◽  
Reduced Intensity

Abstract [Background] Non-myeloablative regimens have been proven to allow engraftment following allogeneic stem cells transplantation with minimal procedure-related toxicity and lower costs. Cord blood has emerged as an appealing alternative source of hematopoietic stem cells for unrelated donor transplantation, but delayed engraftment and frequent transfusion were reported. No studies have formally evaluated the cost of reduced-intensity cord blood transplantation (RICBT). [Purpose] To evaluate the relationship among costs, baseline patient characteristics, and major complications of RICBT, we performed an economic analysis of data in a clinical trial of RICBT for hematologic diseases at a single institution. [Patients and Methods] Ninety-three patients with hematological diseases (median age, 55y; range, 17–79: median body weight, 53kg; range, 38–75) underwent RICBT from March 2002 to May 2004 in Toranomon Hospital. Mean follow-up period was 77 days (range, 13–863). Data on resource use, including hospitalizations, medical procedures, medications, and diagnostic tests, were abstracted from subjects’ clinical trial records. Resources were valued using the Japanese national insurance reimbursement system for inpatient costs at one hospital and average wholesale prices for medications. Monthly costs were calculated and stratified by treatment group and clinical phase. [Results] The median initial inpatient cost was $80,400 (range, 41,300–154,700). When baseline variables were considered, disease status was significant predictor of costs. When clinical events were considered, in-hospital death was associated with higher costs. The mean length of total inpatient days was 78 days (range, 31–222), and the mean length of inpatient days post transplant was 51 days (range, 15–131). The mean units of transfused RBC, Platelet, and FFP were 27u, 224u, and 27u, respectively. [Discussion] This study firstly demonstrates that the cost of RICBT was much higher as compared to previous RIST using peripheral blood or bone marrow. RICBT is an attractive therapy, however, economic problem lies before prevalence of RICBT. The increased numbers of transfusions and supportive care would have effects on costs. The association between mortality and higher costs suggest that prevention of clinical complication may have significant economic benefits. Interventions that decrease these complications may have favorable cost-benefit ratios, and will be the focus of future investigation.

scholarly journals Human Application of Ex Vivo Expanded Umbilical Cord-Derived Mesenchymal Stem Cells: Enhance Hematopoiesis after Cord Blood Transplantation

2013 ◽  
Vol 22 (11) ◽  
pp. 2041-2051 ◽  
Author(s):  
Kang-Hsi Wu ◽  
Chris Tsai ◽  
Han-Ping Wu ◽  
Martin Sieber ◽  
Ching-Tien Peng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Ex Vivo ◽  
Cord Blood Transplantation ◽  
Blood Transplantation

Increased Engraftment after Double Cord Blood Transplantation in NOD/SCID Mice.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1199-1199
Author(s):  
Alma J. Nauta ◽  
Alwine B. Kruisselbrink ◽  
Roelof Willemze ◽  
Willem E. Fibbe
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Human Platelets ◽  
Hematopoietic Stem ◽  
Cell Dose ◽  
Blood Transplantation ◽  
Cd34 Cells

Abstract Umbilical cord blood (UCB) is considered as an attractive alternative source of hematopoietic stem cells for allogeneic stem cell transplantations in patients who lack HLA-matched donors. However, the low cell dose adversely affects the speed of hematopoietic recovery and therefore limits the application of UCB transplantation in adults. Although ex-vivo expansion of cord blood cells has been explored as a strategy to increase the cell dose, compromised engraftment potential of expanded cells has been demonstrated. Another approach to overcome cell dose limitations is transplantation of multiple, unrelated UCB units. To investigate the effect of multiple cord transplantation on engraftment, NOD/SCID mice were transplanted with human hematopoietic progenitor cells (CD34+) derived from two UCB units with HLA disparity. During the first six weeks after transplantation the number of human platelets in peripheral blood was quantified by flow cytometry. Six weeks after transplantation, the mice were sacrificed and the percentage and donor origin of human CD45+ cells in blood, and in bone marrow was determined by flow cytometry. Transplantation of CD34+ cells derived from two UCB donors resulted in significantly higher number of human platelets in peripheral blood than transplantation of CD34+ cells from either donor alone, ranging from 3.92x106/ml to 10.29x106/ml (mean 6.4x106 ± 2.55x106/ml) and 0.11x106/ml to 3.12.106/ml (mean 1.42x106 ± 1.17x106/ml), respectively. Furthermore, the overall human cell engraftment level in bone marrow after double cord blood transplantation ranged from 7.01% to 64.34% (mean 29.6 ± 21.5%) a nearly 7-fold increase compared to single cord blood transplantation ranging from 0.27% to 13.5% (mean 4.6 ± 3.8%) Although consistently higher engraftment levels were reached after double cord blood transplantation, two different patterns were observed: in 2 out of 4 experiments cells from one donor predominated the engraftment (ratio 3:1), while in two other experiments the two units contributed equally to BM engraftment. The mechanism underlying these effects are <S>is</S> not yet clear. It is not very likely that the single donor predominance results from an unequal amount of hematopoietic stem cells in the cord blood units because each cord blood showed comparable levels of engraftment as a single unit. Alternatively, the unequal engraftment may result from an immunological competition or a graft versus graft stimulatory effect between the cords during the engraftment process and further studies are required to determine if the contribution of both units is dependent on the degree of HLA matching between the two cords. Taken together, these results demonstrate that double cord blood transplantation may represent a means of achieving increased engraftment, making multiple cord blood transplantation a promising strategy to improve the outcome of UCB transplantation. Studies are underway to unravel the mechanisms underlying the enhanced engraftment.

Second Transplant with HLA Haplo-Identical Hematopoietic Stem Cells for Graft Failure after Double Units Cord Blood Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5058-5058
Author(s):  
Wen Yao ◽  
Zimin Sun ◽  
Huilan Liu ◽  
Xingbing Wang dortor ◽  
Zuyi Wsng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cord Blood ◽  
Graft Failure ◽  
Cord Blood Transplantation ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Blood Transplantation ◽  
Second Transplantation ◽  
Cd34 Cells ◽  
Double Units

Abstract Graft failure (GF) can be a fatal complication following cord blood transplantation (CBT). Up to date, there has not been an ideal treatment for it. Recently, second transplant has been used as a potential therapy for treatment of GF. However, it is unclear which is the best source for donor cells that result successful engraftment and low rate of complications related to transplantation. In this study, we evaluated the outcomes and safety of second transplant with HLA haplo-identical hematopoietic stem cells for graft failure after double units cord blood transplantation in three patients. These patients suffered from myelodysplasia (MDS), acute lymphoblastic leukemia (ALL), severe aplastic anemia (SAA) respectively (median age, 16 years; range, 10–20 years). After myeloablative conditioning, all of them received double umbilical cord blood (UCB) units with at least one 5/6 HLA-matched unit (median infused dose, 6.85×107 nucleated cell [NC]/kg; range, 6.28–7.17×107 NC/kg). The characteristics of these patients and double cord blood transplantation data are detailed in the following Table. The former two patients developed early GF on 30 days after CBT. In the third patient, neutrophil and platelet recovery was observed on +14d and +31d respectively, and sustained hamatopoiesis was derived from a single donor with higher nucleated and CD34+ cells until 4 months after CBT when late GF happened, After reduced-intensity or myeloablative conditioning, all of them subsequently received HLA haplo-identical three-loci mismatched HSCT donated by their mothers (median infused dose, 8.40×108 nucleated cell [NC]/kg; range, 8.02–9.82×107 NC/kg). The time interval from GF to the second transplantation of these patients ranged from 7 to 10 days. Cyclosporine A (CsA) and mycophenolate mofetil (MMF) were ad- ministered for the prophylaxis of graft-versus-host disease (GVHD). Detailed data of the second transplantation were also shown below. Engraftment was achieved on all three patients between the twelfth day and the fourteenth day after the transplantation with a full donor chimaerism. Acute GVHD of grades I–II and slight chronic GVHD occurred in these patients. All three patients survive up till now, and one patient has survived for 15 months after the second transplantation. This is the first report in china using HLA haplo-identical HSCT to rescue the GF after double CBT in China. The results are encouraging though the number of the patients is too small. Patients’characteristics and transplantation data Patients No. 1 No. 2 No. 3 Age(years)/sex 20/F 10/M 16/F Body weight 43.5kg 32kg 40kg Diagnosis MDS ALL(CR1) SAA Conditioning Ara-c/CY/TBI BU/CY CY/ATG Nucleated cells (CB1/CB2) (4.02/2.83)×107/kg (3.92/2.36)×107/kg (2.44/4.73)×107/kg CD34+ cells (CB1/CB2) (0.61/0.28)×105/kg (2.55/0.85)×105/kg (0.53/1.42)×105/kg CD3+ cells (CB1/CB2) (2.26/2.34)×106/kg (0.37/0.16)×106/kg (0.53/0.35)×106/kg HLA-mismatched (CB1; CB2) 2/6; 1/6. 1/6; 0/6 0/6; 1/6 GF 30d 30d 4m Second transplant 37d 38d 4m Conditioning Flu/ATG TBI2GY/ATG Flu/CY/ATG GVHD prhphylaxis CsA+MMF CsA+MMF CsA+MMF Nucleated cells 8.02×108/kg 8.40×108/kg 9.82×108/kg CD34+ cells 4.31×106/kg 3.50×106/kg 7.86×106/kg ANC>0.5×109/L 12d 13d 14d PLT>2×109/L 18d 17d 18d Follow up 15M+ 3M+ 12M+

In Vitro Assessment of Tolerance and Rejection Occurring After Co-Transplantation of Allogeneic Umbilical Cord Blood and Haploidentical CD34+ Cells as Treatment for Severe Aplastic Anemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2352-2352
Author(s):  
Nicole J. Gormley ◽  
Aleah Smith ◽  
Maria Berg ◽  
Lisa Cook ◽  
Catalina Ramos ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Neutrophil Recovery ◽  
Post Transplant ◽  
Blood Transplantation ◽  
Cd34 Cells ◽  
Cord Blood Cells

Abstract Abstract 2352 Introduction/Methods: The administration of highly purified haploidentical peripheral blood CD34+ cells combined with an unrelated cord blood transplant results in earlier neutrophil engraftment than is typically seen with a cord blood transplant alone. Chimerism data from pilot trials evaluating this strategy have reported 3 phases of engraftment: 1) early myeloid engraftment from transplanted haplo-CD34+ cells followed by 2) cord blood engraftment resulting in dual chimerism and 3) the subsequent disappearance of haploidentical donor cells with resultant full donor cord chimerism. The mechanism accounting for the disappearance of haploidentical cells has not been defined. Here the clinical results and an in vitro assessment of alloreactivity in three patients that underwent combined haploidentical CD34+ cell and cord blood transplantation for severe aplastic anemia (SAA) are described. The conditioning regimen consisted of cyclophosphamide (60mg/kg/day on days -7 and -6), fludarabine (25mg/m2/day on days -5 to -1), horse ATG (40mg/kg/day on days -5 to -2), and total body irradiation (200cGy on day -1). GVHD prophylaxis consisted of tacrolimus and mycophenolate mofetil. PCR of STRs was used to assess chimerism in T-cell and myeloid lineages and mixed lymphocyte reaction assays(MLR) were performed on peripheral blood samples collected at different time-points post-transplant to assess for alloreactivity against the recipient, the haploidentical donor, or the cord unit. Stimulator cord blood cells for the MLR were obtained from residual cord blood cells remaining in the infusion bag after patient administration and expanded in vitro using anti-CD28/CD3 Dynabeads. Results: Prior to transplantation, all three pts had transfusion dependent SAA associated with severe neutropenia that was refractory to conventional immunosuppressive therapy. Pt 1 had an early transient myeloid recovery (ANC 400 on day+11) from the haploidentical donor followed by engraftment of the cord unit (Cord ANC > 500) on day 21. The patient is currently 2 years post transplant and has 100% cord blood chimerism and is transfusion independent. An MLR assay performed when donor T-cell chimerism was 100% cord, showed evidence for rejection of the haploid cells by cord blood T-cells, with the MLR response to haploidentical donor cells being seven fold higher than the response to fully HLA-mismatched 3rd party cells. In pt 2, neutrophil recovery from the transplanted haploidentical donor occurred on day +10, with chimerism studies showing no evidence for cord engraftment in either myeloid or T-cell lineages at any point post-transplant. The patient is currently 15 months post transplant and is transfusion independent with normal blood counts and sustained “split” chimerism (T-cells recipient in origin with myeloid cells being 100% haploidentical donor). MLR assays showed that the recipient was tolerant to the haploid donor, with no statistically significant difference in the alloreactive response to the haploid donor compared to self. In pt 3, neutrophil recovery from the transplanted haploidentical donor occurred on day +10, with chimerism studies showing split chimerism (T-cell chimerism >90% cord and myeloid chimerism 88–100% haploid donor in origin). MLR assays again showed evidence of rejection of the haploid cells by cord blood T-cells, with a trend towards greater alloreactivity against the haploid donor compared to an HLA mismatched 3rd party on post-transplant day +63. Conclusions: Combined haploidentical CD34+ cell and unrelated cord blood transplantation following highly immunosuppressive conditioning represents a viable treatment option for patients with SAA who lack an HLA-matched donor. Using this approach, 2 of 3 pts had cord blood engraftment associated with early neutrophil recovery from the haploidentical donor. In one pt, the cord unit failed to engraft. Remarkably, sustained engraftment from the haploidentical donor in this pt resulted in transfusion independence. MLR appears to be a useful approach to assess the in vitro alloreactivity of this unique stem cell graft source. In the two pts who had cord engraftment, in vitro MLR assessments established that the disappearance of haploid cells occurred as a consequence of rejection of the haploidentical cells by engrafting cord blood T-cells, rather than from non-immunological haploidentical cell graft failure. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Phase I study of cord blood transplantation with intrabone marrow injection of mesenchymal stem cells

Medicine ◽  
2018 ◽  
Vol 97 (17) ◽  
pp. e0449 ◽  
Author(s):  
Tatsunori Goto ◽  
Makoto Murata ◽  
Seitaro Terakura ◽  
Tetsuya Nishida ◽  
Yoshiya Adachi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Phase I ◽  
Cord Blood ◽  
Phase I Study ◽  
Cord Blood Transplantation ◽  
Blood Transplantation
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