Human adipose stromal cells expanded in human serum promote engraftment of human peripheral blood hematopoietic stem cells in NOD/SCID mice

2005 ◽  
Vol 329 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Su Jin Kim ◽  
Hyun Hwa Cho ◽  
Yeon Jeong Kim ◽  
Su Yeong Seo ◽  
Han Na Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Human Serum ◽  
Stromal Cells ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Scid Mice ◽  
Adipose Stromal Cells ◽  
Hematopoietic Stem

YM477, a Novel Orally-Active Thrombopoietin Receptor Agonist.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2298-2298 ◽  
Author(s):  
Ken-ichi Suzuki ◽  
Masaki Abe ◽  
Mari Fukushima-Shintani ◽  
Keizo Sugasawa ◽  
Fukushi Hirayama ◽  
...  
Keyword(s):  
Stem Cells ◽  
Platelet Count ◽  
Hematopoietic Stem Cells ◽  
Peripheral Blood ◽  
Receptor Agonist ◽  
Human Platelet ◽  
Human Platelets ◽  
Scid Mice ◽  
Hematopoietic Stem ◽  
Orally Active

Abstract Thrombopoietin (TPO) is the principal physiologic regulator of platelet production. The search for an orally-active nonpeptidyl small molecule TPO receptor agonist has resulted in the discovery of YM477. YM477 acted specifically on the TPO receptor and stimulated megakaryocytopoiesis throughout the development and maturation of megakaryocytes just as TPO does. YM477, however, was shown to have high species specificity, effective in only humans and chimpanzees. Recently, nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice were characterized as an efficient engraftment model for human hematopoietic stem cells, as this model results in the production of human platelets. In this way, we examined the in vivo platelet-increasing effect of YM477 in human platelet-producing NOD/SCID mice in which human hematopoietic stem cells were transplanted. In this study, we used commercially available cryopreserved human fetal liver CD34+ cells as a source of human hematopoietic stem cells. The cells were transplanted into sublethally irradiated (240 cGy) NOD/SCID mice. Human platelets started to appear in peripheral blood of these mice 4 weeks after transplantation. The production of human platelets continued up to one year post-transplant. Various doses of YM477 (0, 0.3, 1, and 3 mg/kg/day) were orally administered for 14 days to NOD/SCID mice that had been confirmed to produce human platelets stably. Oral administration of YM477 dose-dependently increased the number of human platelets produced by these mice, with significance at 1 mg/kg/day and above. The increase in the human platelet count reached about 2.7-fold at 1 mg/kg/day and about 3.0-fold at 3 mg/kg/day on day 14. Withdrawal of YM477 administration caused the human platelet count to return to the pretreatment level. The number of murine platelets did not change during the study period. Next, to evaluate the function of human platelets produced in peripheral blood of these mice, the expression of activation-dependent marker CD62P (P-selectin) on human platelets stimulated with thrombin receptor agonist peptide (TRAP) were examined. CD62P expression on human platelets was induced by the stimulation of blood from transplanted mice with TRAP, suggesting that human platelets produced in NOD/SCID mice were functional. Furthermore, the maximum response of CD62P expression on human platelets induced by TRAP was evaluated before and after administration of YM477 at 3 mg/kg/day for 14 days. CD62P expression was not changed by administration of YM477, which was similar to the results obtained with a vehicle group. These results suggest that YM477 is an orally active TPO receptor agonist useful for treating patients with thrombocytopenia.

Separation of hematopoietic stem cells from human peripheral blood through modified polyurethane foaming membranes

2008 ◽  
Vol 85A (4) ◽  
pp. 853-861 ◽  
Author(s):  
Akon Higuchi ◽  
Mayu Sekiya ◽  
Yumiko Gomei ◽  
Masaru Sakurai ◽  
Wen-Yih Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Hematopoietic Stem ◽  
Polyurethane Foaming

Third-generation, self-inactivating gp91phoxlentivector corrects the oxidase defect in NOD/SCID mouse–repopulating peripheral blood–mobilized CD34+ cells from patients with X-linked chronic granulomatous disease

Blood ◽  
2002 ◽  
Vol 100 (13) ◽  
pp. 4381-4390 ◽  
Author(s):  
Joachim Roesler ◽  
Sebastian Brenner ◽  
Anatoly A. Bukovsky ◽  
Narda Whiting-Theobald ◽  
Thomas Dull ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Chronic Granulomatous Disease ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
Scid Mice ◽  
Granulomatous Disease ◽  
In Vivo Evaluation ◽  
Hematopoietic Stem

HIV-1–derived lentivectors are promising for gene transfer into hematopoietic stem cells but require preclinical in vivo evaluation relevant to specific human diseases. Nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice accept human hematopoietic stem cell grafts, providing a unique opportunity for in vivo evaluation of therapies targeting human hematopoietic diseases. We demonstrate for the first time that hematopoietic stem cells from patients with X-linked chronic granulomatous disease (X-CGD) give rise to X-CGD–phenotype neutrophils in the NOD/SCID model that can be corrected using VSV-G–pseudotyped, 3rd-generation, self-inactivating (SIN) lentivector encoding gp91phox. We transduced X-CGD patient-mobilized CD34+ peripheral blood stem cells (CD34+PBSCs) with lentivector–gp91phox or amphotropic oncoretrovirus MFGS–gp91phox and evaluated correction ex vivo and in vivo in NOD/SCID mice. Only lentivector transduced CD34+PBSCs under ex vivo conditions nonpermissive for cell division, but both vectors performed best under conditions permissive for proliferation (multiple growth factors). Under the latter conditions, lentivector and MFGS achieved significant ex vivo correction of X-CGD CD34+PBSCs (18% and 54% of cells expressing gp91phox, associated with 53% and 163% of normal superoxide production, respectively). However, lentivector, but not MFGS, achieved significant correction of human X-CGD neutrophils arising in vivo in NOD/SCID mice that underwent transplantation (20% and 2.4%, respectively). Thus, 3rd-generation SIN lentivector–gp91phox performs well as assessed in human X-CGD neutrophils differentiating in vivo, and our studies suggest that the NOD/SCID model is generally applicable for in vivo study of therapies evaluated in human blood cells expressing a specific disease phenotype.

A Review of Evaluating Hematopoietic Stem Cells Derived from Umbilical Cord Blood's Expansion and Homing

2020 ◽  
Vol 15 (3) ◽  
pp. 250-262
Author(s):  
Maryam Islami ◽  
Fatemeh Soleimanifar
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Umbilical Cord ◽  
Stromal Cells ◽  
Ex Vivo ◽  
Hematologic Malignancies ◽  
Future Directions ◽  
Hematopoietic Stem ◽  
Efficient Procedure ◽  
Hematopoietic Recovery

Transplantation of hematopoietic stem cells (HSCs) derived from umbilical cord blood (UCB) has been taken into account as a therapeutic approach in patients with hematologic malignancies. Unfortunately, there are limitations concerning HSC transplantation (HSCT), including (a) low contents of UCB-HSCs in a single unit of UCB and (b) defects in UCB-HSC homing to their niche. Therefore, delays are observed in hematopoietic and immunologic recovery and homing. Among numerous strategies proposed, ex vivo expansion of UCB-HSCs to enhance UCB-HSC dose without any differentiation into mature cells is known as an efficient procedure that is able to alter clinical treatments through adjusting transplantation-related results and making them available. Accordingly, culture type, cytokine combinations, O2 level, co-culture with mesenchymal stromal cells (MSCs), as well as gene manipulation of UCB-HSCs can have effects on their expansion and growth. Besides, defects in homing can be resolved by exposing UCB-HSCs to compounds aimed at improving homing. Fucosylation of HSCs before expansion, CXCR4-SDF-1 axis partnership and homing gene involvement are among strategies that all depend on efficiency, reasonable costs, and confirmation of clinical trials. In general, the present study reviewed factors improving the expansion and homing of UCB-HSCs aimed at advancing hematopoietic recovery and expansion in clinical applications and future directions.

scholarly journals Human amniotic mesenchymal stromal cells support the ex vivo expansion of cord blood hematopoietic stem cells

2021 ◽  
Author(s):  
Valentina Orticelli ◽  
Andrea Papait ◽  
Elsa Vertua ◽  
Patrizia Bonassi Signoroni ◽  
Pietro Romele ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Cord Blood ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Hematopoietic Stem

scholarly journals Long-term repopulating hematopoietic stem cells and “side population” in human steady state peripheral blood

2013 ◽  
Vol 11 (1) ◽  
pp. 625-633 ◽  
Author(s):  
Philippe Brunet de la Grange ◽  
Marija Vlaski ◽  
Pascale Duchez ◽  
Jean Chevaleyre ◽  
Veronique Lapostolle ◽  
...  
Keyword(s):  
Stem Cells ◽  
Steady State ◽  
Hematopoietic Stem Cells ◽  
Peripheral Blood ◽  
Side Population ◽  
Hematopoietic Stem
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