scholarly journals Relative frequency of immature CD34+/CD90+ subset in peripheral blood following mobilization correlates closely and inversely with the absolute count of harvested stem cells in multiple myeloma patients

2017 ◽  
Vol 74 (11) ◽  
pp. 1071-1077 ◽  
Author(s):  
Bela Balint ◽  
Ivan Stanojevic ◽  
Milena Todorovic ◽  
Dragana Stamatovic ◽  
Mirjana Pavlovic ◽  
...  
Keyword(s):  
Stem Cells ◽  
Peripheral Blood ◽  
Relative Frequency ◽  
Inverse Correlation ◽  
Absolute Count ◽  
Cell Region ◽  
Hematopoietic Recovery ◽  
Cd34 Cells ◽  
The Absolute ◽  
Sequential Gating

Background/Aim. Stem cells (SCs) guarantee complete/longterm bone marrow (BM) repopulation after SC-transplants. The aim of the study was to evaluate absolute count of total SCs (determined by ISHAGE-sequential-gating protocol ? SCish) and relative frequency of immature CD34+/CD90+ (CD90+SCish) subset in peripheral blood (PB) as predictive factors of mobilization and apheresis product (AP) quality. Methods. Mobilization included chemotherapy and granulocytegrowth- factor (G-CSF). Harvesting was performed by Spectra- Optia-IDL-system. The SCsish were determined as a constitutional part of CD34+ cells in the ?stem-cell-region? using FC- 500 flow-cytometer. In this study, the original ISHAGEsequential- gating protocol was modified by introduction of anti-CD90-PE monoclonal-antibody into the analysis of CD90 expression on SCish (CD90+SCish). The results were presented as a percentage of SCish per nucleated-cell count, absolute SCish count in ?L of the PB or the AP, percentage of the CD90+SCish expressed to SCish and absolute CD90+SCish count in ?L of the PB or the AP. Results. The absolute count of total SCish and CD90+SCish was significantly higher (p = 0.0007 and p = 0.0266, respectively) in the AP than in the PB samples. The CD90+SCish/total SCish indexes from PB were higher than indexes from the AP (p = 0.039). The relative frequency of CD90+SCish showed a highly significant inverse correlation with the absolute count of total SCish in both, the PB and AP (p = 0.0003 and p = 0.0013 respectively). The relative frequency of CD90+SCish from the PB also showed a significant (p = 0.0002) inverse relationship with total SCish count in the AP. Patients with less than 10% CD90+SCish in the PB had evidently higher (p = 0.0025) total SCish count in the AP. Conclusion. We speculate that lower CD90+SCish yield in the AP is not a consequence of an inferior collection efficacy, but most likely a result of several still not fully resolved immature SC cytomorphological/ biophysical features. Therefore, following the mobilization by chemotherapy G-CSF, some logical questions appear ? whether we should follow the absolute count of total SCish, or, whether we should test for relative frequency of CD90+SCish prior to harvesting. To reach the final conclusions, it is essential to conduct further controlled and larger investigations concerning the correlation of circulating and harvested SCs with patients' hematopoietic recovery.

scholarly journals Factors Associated with Successful Mobilization and Collection of Peripheral Blood Hematopoietic Stem Cells in Autologous and Allogeneic Donors

2017 ◽  
Vol 2017 ◽  
pp. 1
Author(s):  
Rada Grubovic ◽  
Borce Georgievski ◽  
Lidija Cevreska ◽  
Sonja Genadieva-Stavric ◽  
Milos R. Grubovic
Keyword(s):  
Stem Cells ◽  
Platelet Count ◽  
Hematopoietic Stem Cells ◽  
Peripheral Blood ◽  
Inverse Correlation ◽  
Hematopoietic Stem ◽  
Laboratory Parameters ◽  
Cd34 Cells ◽  
Number Of Cycles ◽  
Poor Mobilizers

BACKGROUND: Peripheral blood hematopoietic stem cells (PBSC) have largely replaced bone marrow derived stem cells in autologous transplantations, and have become the preferred source of stem cells in the majority of allogeneic transplantations. Sufficient number of mobilized and collected hematopoietic stem cells (HSC) is needed for successful hematopoietic stem cell transplantation.MATERIAL AND METHOD: This study was performed in the Institute for Transfusion Medicine of RM and the University Clinic of Hematology from 2008 till 2016. There were 30 allogeneic and 90 autologous donors that underwent mobilization and collection of PBSC. The association between possible predictive factors such as demographic characteristics, laboratory parameters and collection parameters in both groups, and mobilization strategy and clinical characteristics in autologous donors and number of collected PBSC was analyzed.RESULTS: There were 226 apheresis, 182 in autologous donors (mean 2, range 1-3) and 44 apheresis in 30 allogeneic donors (mean 1.5, range 1-2). The mean number of collected MNC in autologous donors was 3.09 x 108/kg and 2.85 x 106/kg CD34+ cells, and 3.23 x 108/kg MNC and 3.20 x 106/kg CD34+ cells in allogeneic donors. Significantly larger number of MNC and CD34+ cells was collected with the WBC set. There was a statistically significant correlation between the total number of collected MNC in autologous donors and platelet count before mobilization, the number of cycles in one apheresis procedure, quantity of collected graft and the number of collected MNC and CD34+ cells on the first day of harvestration. There was a statistically significant correlation between the total number of collected MNC in allogeneic donors and platelet count before mobilization, the number of cycles in one apheresis procedure, quantity of collected graft and number of MNC on first day of harvestration. There was a strong correlation between the number of collected MNC and CD34+ cells on the first harvest and the total number of collected MNC and CD34+ cells in poor mobilizers, and inverse correlation with the number of apheresis procedures. Donors who donated MNC ≤ 0.7 x 108/kg and/or ≤ 0.7 x 106/kg CD34+ cells on the first harvest (84.6%) were strong predictors of poor mobilizers.CONCLUSION: Determining the proper level of baseline and preaheresis laboratory parameters for initiating mobilization and apheresis procedure which is safe for donors and greatly efficient in collection of PBSC is needed for optimization of these procedures, as well as for early intervention in poor mobilizers.

An Effective Hematopoietic Stem Cell Mobilization Algorithm for Adding Plerixafor to G-CSF for Multiple Myeloma Patients Undergoing Autologous Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4389-4389 ◽  
Author(s):  
Justin LaPorte ◽  
Scott R. Solomon ◽  
Asad Bashey ◽  
H. Kent Holland ◽  
Lawrence E. Morris ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Cell Count ◽  
Hematopoietic Stem Cell ◽  
Peripheral Blood ◽  
Small Sample ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
The Absolute

Abstract Abstract 4389 Background: Autologous hematopoietic stem cell transplantation (ASCT) has become an integral part of the treatment for multiple myeloma (MM). In addition, it is standard practice to collect enough stem cells for more than one transplant. Therefore, it is critical to have an effective mobilization strategy in order to efficiently collect sufficient numbers of CD34+ cells. Administering granulocyte-colony stimulating factor (G-CSF) alone to MM patients can produce sufficient CD34+ yields in the majority of patients. However, some patients may require > 4 apheresis days to achieve those yields. In addition, some patients may fail to collect enough CD34+ cells for ASCT. Plerixafor was approved in 2008 to be used in combination with G-CSF to mobilize hematopoietic stem cells to the peripheral blood. Plerixafor can increase the average daily CD34+ yields by 3-fold. However, since the majority of patients can collect with G-CSF alone, a plerixafor algorithm was developed in 2009 to judiciously administer plerixafor only to those patients at higher perceived risk for mobilization failure. Administration of plerixafor is based on a peripheral blood CD34+ count drawn after 3 days of G-CSF and subsequent CD34+ collection yields. Methods: G-CSF 10mcg/kg/day (given daily or divided into twice daily) was administered subcutaneously from day 1 to 4. On day 4, a peripheral absolute CD34+ cell count was drawn. If the absolute CD34+ cell count was ≥ 12 cells/mm3 then apheresis started on day 5. If the absolute CD34+ cell count on day 4 was < 12 cells/mm3 plerixafor 240mcg/kg was administered subcutaneously the evening prior to apheresis beginning on day 5. During apheresis, if the CD34+ yield was < 1.0×106 CD34+/kg or 50% less than the previous collection, plerixafor was initiated. The minimum collection yield for all patients was 4.0×106 CD34+/kg. The maximum number of apheresis days was 5. Previous therapy was also examined. Results: From October 2009 to May 2011, 68 multiple myeloma patients were mobilized with G-CSF +/− plerixafor. Ninety-three percent (63/68) of patients achieved the minimum collection yield of 4.0×106 CD34+/kg. Ninety-nine percent (67/68) of patients achieved a yield of at least 2.0×106 CD34+/kg. Forty-four percent (30/68) of the patients required at least 1 dose of plerixafor with the majority requiring it prior to the first apheresis (83%). The median days of apheresis was 2 (range 1–5). The overall average yield on the first apheresis day was 4.35×106 CD34+/kg (95% CI +/− 0.64). The overall average total yield was 8.71×106 CD34+/kg (95% CI +/− 0.93). Sixty percent (41/68) and 76% (52/68) of patients collected ≥ 6.0×106 CD34+/kg in ≤ 2 days and ≤ 4 days of apheresis, respectively. The average daily yield (ACD34) for G-CSF alone can be predicted by ACD34 = 0.0377+ 0.07456xCD34 (see figure). ACD34 after plerixafor + G-CSF can be predicted by the equation 3(0.0377 + 0.07456xCD34) = ACD34. Of the patients that received previous radiation therapy (9) or cyclophosphamide (2), plerixafor was utilized in 78% and 100%, respectively. Previous lenalidomide therapy was present in 50% of the patients and it did not correlate to any increase in plerixafor usage. Conclusion: Adding plerixafor to G-CSF based upon a day 4 CD34+ count and collection yields is an effective strategy to mobilize CD34+ cells. Ninety-three percent of the of the patients were able to collect a minimum of 4.0×106 CD34+/kg cells and 99% collected > 2.0×106 CD34+/kg, in a median of two collections. Limitations to the study include a small sample size and an arbitrarily determined threshold to administer plerixafor. Also, the length of lenalidomide could not be retrospectively determined. A cost-based analysis is currently being performed to help determine the best day 4 CD34 cutoff for future studies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Transplantation of allogeneic CD34+ peripheral blood stem cells in patients with advanced hematologic malignancy

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4132-4138 ◽  
Author(s):  
WI Bensinger ◽  
CD Buckner ◽  
K Shannon-Dorcy ◽  
S Rowley ◽  
FR Appelbaum ◽  
...  
Keyword(s):  
Stem Cells ◽  
Body Weight ◽  
Peripheral Blood ◽  
Hematologic Malignancy ◽  
Chronic Gvhd ◽  
Allogeneic Transplantation ◽  
Hematologic Malignancies ◽  
Peripheral Blood Stem Cells ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract Sixteen patients with advanced hematologic malignancies were transplanted with HLA-identical allogeneic peripheral blood stem cells (PBSCs) that were selected for CD34+ cells by an avidin-biotin immunoadsorption technique. The median age of patients was 48 years (range, 37 to 67). Patients received 12.0 or 13.2 Gy of total body irradiation followed by 120 mg/kg of cyclophosphamide. Normal donors received 16 mg/kg of granulocyte-colony stimulating factor on days 1 to 6 followed by PBSC harvests on days 4 to 7. PBSC harvests were processed each day on a single avidin-blotin column containing an antibody to the CD34 antigen and processed cells were infused without cryopreservation daily for 4 consecutive days. Prophylaxis against graft-versus-host disease (GVHD) consisted of cyclosporine alone for 5 patients and CSA plus methotrexate for 11 patients. A median of 18.64 (6.74 to 34.97) x 10(8) CD34+ cells/kg patient body weight were collected from each donor. A median of 8.96 (2.62 to 17.34) x 10(8) CD34+ cells/kg patient body weight were recovered after avidin-biotin adsorption which represented a median CD34+ cell yield of 53% (18% to 77%) with a median purity of 62% (34% to 82%). There was a reduction in CD3+ cells from a median of 557.26 (227.73 to 677.77) x 106/kg to 0.73 x 10(4)/kg (0.40 to 3.65), in CD4+ cells from 351.72 (194.47 to 520.11) x 10(6)/kg to 0.40 (0.15 to 1.03) x 10(4)/kg and in CD8+ cells from 169.74 (53.34 to 325.83) x 10(6)/ kg to 0.32 (0.12 to 2.71) x 10(4)/kg representing a median 2.8 (2.19 to 3.14) log reduction in T cells. One patient died of infection on day 3 posttransplant and was unevaluable for recovery of neutrophils. The median day to recovery of 500 neutrophils/mL was 15 (8 to 26) in the remaining 15 patients. Six of 16 patients falled to achieve a platelet count of 20,000/mL before death on days 3 to 97 of transplant-related complications. The median day to achieving platelets of 20,000 mL in the remaining 10 patients was 11 (7 to 31). Eight of 16 patients (50%) died between 3 and 97 days posttransplant, 7 of transplant-related causes, and 1 of progressive disease. Grade 2–4 acute GVHD occurred in 12 out of 14 (86%) and grades 3–4 in 6 out of 14 (43%) evaluable patients. Six of 8 evaluable patients developed clinical chronic GVHD and 1 developed subclinical chronic GVHD. Bone marrow and/or peripheral blood chimerism studies in 12 evaluable patients showed 97% to 100% donor type in 11 patients with 1 patient in relapse showing 40% donor cells 60 to 90 days posttransplant. Four of 16 patients (25%) are alive and disease-free 312 to 576 days after transplant. There were no episodes of graft failure or rejection. This study shows that allogeneic transplantation using CD34+ selected PBSC results in prompt and sustained engraftment. CD34+ selection, as employed in this preliminary study, however, resulted in an apparently higher rate of acute and chronic GVHD. However, The sample size is quite small and precludes a more definitive conclusion regarding GVHD.

scholarly journals Differential effects of recombinant thrombopoietin and bone marrow stromal-conditioned media on neonatal versus adult megakaryocytes

Blood ◽  
2006 ◽  
Vol 108 (10) ◽  
pp. 3360-3362 ◽  
Author(s):  
Karen M. Pastos ◽  
William B. Slayton ◽  
Lisa M. Rimsza ◽  
Linda Young ◽  
Martha C. Sola-Visner
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Peripheral Blood ◽  
Conditioned Media ◽  
Valuable Source ◽  
Cd34 Cells ◽  
Adult Bone

Abstract Umbilical cord blood (CB) is a valuable source of stem cells for transplantation, but CB transplantations are frequently complicated by delayed platelet engraftment. The reasons underlying this are unclear. We hypothesized that CB- and peripheral-blood (PB)–derived megakaryocytes (MKs) respond differently to the adult hematopoietic microenvironment and to thrombopoietin (Tpo). To test this, we cultured CB- and PB-CD34+ cells in adult bone marrow stromal conditioned media (CM) or unconditioned media (UCM) with increasing concentrations of recombinant Tpo and compared the effects of these conditions on CB-versus PB-MKs. PB-MKs reached highest ploidy in response to UCM + 100 ng/mL rTpo, and the addition of CM inhibited their maturation. In contrast, CB-MKs reached highest ploidy in CM without rTpo, and high rTpo concentrations (> 0.1 ng/mL) inhibited their maturation. This is the first evidence that human neonatal and adult MKs have substantially different biologic responses to Tpo and potentially to other cytokines.

Transplantation of Peripheral Blood Stem Cells Mobilized by Chemotherapy and Single Dose Pegylated G-CSF in Patients with Multiple Myeloma: Equivalence of 6 mg and 12 mg Pegfilgrastim.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2868-2868 ◽  
Author(s):  
Ingmar Bruns ◽  
Ulrich Steidl ◽  
Christof Scheid ◽  
Kai Hübel ◽  
Roland Fenk ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Single Dose ◽  
Peripheral Blood ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cytotoxic Therapy ◽  
Cd 34 ◽  
Cd34 Cells

Abstract To date the most effective treatment for patients (pts) with multiple myeloma consists of conventional induction chemotherapy followed by either single or tandem high-dose chemotherapy and autologous blood stem cell transplantation. Collection of sufficient numbers of hematopoietic stem cells is essential for high-dose chemotherapy. Current regimens for stem cell mobilization are based on daily subcutaneous injections of human recombinant G-CSF starting shortly after cytotoxic therapy. Here we examined the use of polyethyenglycole (PEG)-conjugated G-CSF (pegfilgrastim) at two different doses in patients with stage II or III multiple myeloma. Patients received induction therapy with 2–4 cycles ID or VAD. Following cytotoxic therapy with cyclophosphamide (4g/m2) we administered either a single dose of 6 mg pegfilgrastim (n=10 pts; median age: 55 years), 12 mg pegfilgrastim (n=12 pts; median age: 51 years) or daily doses of 8,5 μg/kg unconjugated G-CSF (filgrastim) (n=12 pts; median age: 51 years). The growth factor was given on day 4 (range 2–5 days) in the “6 mg pegfilgrastim group”, on day 5 (range 2–7 days) in the “12 mg pegfilgrastim group” and on day 4 (range 3–6 days) in the “filgrastim group” after cyclophosphamide. Numbers of CD34+ cells were determined during leukocyte recovery and harvested by large volume apheresis using a cobe spectra blood cell separator. Pegfilgratim was associated with an earlier leukocyte recovery both at the 6mg dose (median 12 days, range 8–16 days) and the 12mg dose (median 12 days, range 7–16 days) as compared to filgrastim (median 14 days, range 11–15 days, p=0.04). Similarily, the peripheral blood CD34+ cell peak occurred earlier in patients who received pegfilgrastim (median 12 days, range 11–18 days versus median 15 days, range 12–18). On the other hand the peripheral blood CD 34+ peak did not differ significantly between the three groups (median 129/μl with 6 mg pegfilgrastim, range 30–433, median 78/μl with 12 mg pegfilgrastim, range 20– 1055 and median 111/μl with filgrastim, range 28–760, p=0.95). With a median of 1.0x10E7 CD34+ cells per kg (range 5.8x10E6-1.9x10E7) in the “6 mg pegfilgrastim group”, 7.4x10E6 CD34+ cells per kg (median, range 4.9x10E6- 3.8x10E7) in the “12 mg pegfilgrastim group” and 10.8x10E6 CD34+ cells per kg (median, range 5.0x10E6-8.7x10E7) in the “filgrastim group” there were no significant differences in the total number of harvested CD34+ cells. Following high-dose therapy with melphalan (200 mg/m2) and autografting leukocyte and platelet reconstitution was similar within all groups. In summary, a single dose of pegfilgrastim after high dose cyclophosphamide is capable of mobilizing a sufficient number of CD 34+ cells for succesful autografting and sustained hematological reconstitution in patients with multiple myeloma. No difference could be observed between 6 mg and 12 mg of pegfilgrastim. Our data provide the basis for randomized studies evaluating the optimal dose and timing of pegfilgrastim as well as long-term outcome in larger cohorts of patients.

Human Embryonic Stem Cell (hESC)-Derived Hematopoietic Elements Are Capable of Engrafting Primary as well as Secondary Fetal Sheep Recipients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2685-2685
Author(s):  
A. Daisy Narayan ◽  
Jessica L. Chase ◽  
Adel Ersek ◽  
James A. Thomson ◽  
Rachel L. Lewis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Peripheral Blood ◽  
Fetal Sheep ◽  
Hematopoietic Stem ◽  
Blood Samples ◽  
Human Dna ◽  
Cd34 Cells ◽  
Hematopoietic Activity

Abstract We used transplantation into 10 and 20 pre-immune fetal sheep recipients (55–65 days-old, term: 145 days) to evaluate the in vivo potential of hematopoietic elements derived from hESC. The in utero human/sheep xenograft model has proven valuable in assessing the in vivo hematopoietic activity of stem cells from a variety of fetal and post-natal human sources. Five transplant groups were established. Non-differentiated hESC were injected in one group. In the second and third group, embroid bodies differentiated for 8 days were injected whole or CD34+ cells were selected for injection. In the fourth and fifth group, hESC were differentiated on S17 mouse stroma layer and injected whole or CD34+ cells were selected for injection. The animals were allowed to complete gestation and be born. Bone marrow and peripheral blood samples were taken periodically up to over 12 months after injection, and PCR and flowcytometry was used to determine the presence of human DNA/blood cells in these samples. A total of 30 animals were analyzed. One primary recipient that was positive for human hematopoietic activity was sacrificed and whole bone marrow cells were transplanted into a secondary recipient. We analyzed the secondary recipient at 9 months post-injection by PCR and found it to be positive for human DNA in its peripheral blood and bone marrow. This animal was further challenged with human GM-CSF and human hematopoietic activity was noted by flowcytometry analyses of bone marrow and peripheral blood samples. Further, CD34+ cells enriched from its bone marrow were cultured in methylcellulose and human colonies were identified by PCR. We therefore conclude that hESC are capable of generating hematopoietic cells that engraft in 1° sheep recipients. These cells also fulfill the criteria for long-term engrafting hematopoietic stem cells as demonstrated by engraftment and differentiation in the 20 recipient.

Contribution of HGF to Liver Regeneration by Strong Mobilization of Bone Marrow Stem Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1680-1680
Author(s):  
Fumihito Tajima ◽  
Hiroyuki Tsuchitya ◽  
Kenichi Nishikawa ◽  
Toshirou Okazaki ◽  
Goushi Shiota
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Liver Regeneration ◽  
Peripheral Blood ◽  
Wild Type Mouse ◽  
Bone Marrow Stem Cell ◽  
Bone Marrow Stem Cells ◽  
Wild Type ◽  
Cd34 Cells ◽  
Marrow Stem Cell

Abstract Cell plasticity of bone marrow stem cells to hepatocytes is known, however, the details are still unclear. hepatocyte growth factor (HGF) promotes an increase in liver stem cells in severely injured liver, but intervention to bone marrow stem cell is unclear. We examined a role of HGF in bone marrow stem cell-mediated liver regeneration in order to obtain effective liver regeneration. First, we found that the phenotype of stem cells, which can differentiate into hepatocytes, is Lin−c-kit+Sca-1+CD34− in bone marrow or Lin−c-kit+Sca−1+CD34+ in peripheral blood mobilized by G-CSF. We transplanted single Lin−c-kit+Sca-1+CD34− bone marrow cell harvested from male EGFP mouse to female wild type mouse, and then, using this GFP-chimera-mouse, we found that bone marrow origin GFP+ and Y chromosome+ hepatic cells were present in liver after acute liver damage. Next, single Lin−c-kit+Sca-1+CD34+ peripheral blood cell, which was mobilized in peripheral blood by administration of G-CSF, was transplanted into the portal vein of the wild type mouse which was given hepatic damage. We found that the GFP-positive cells also expressed albumin. Second, we investigated whether the HGF can mobilize stem cells from bone marrow to peripheral blood. In peripheral blood of HGF transgenic mice, 1.1% developed CD34+ cells and 20±3 colony forming cells of 1X106 peripheral blood mononuclear cells were shown. Colony forming cells were found in the mouse into which an HGF-expressing adenovirus was administered. After injection of rHGF to mice, a significant time-dependent increase of percentage of CD34+ cells in the PB was noted at the first 3 hours and CD34+ cells were increased in dose-dependent manner of rHGF and reached plateau level at 100 m/kg. The mice having transplantation with PB cells from 100 mg HGF-treated mice for 4days showed engraftment 2 months after transplantation. Upon activation of rHGF in mouse MS-5 stromal cells, phosphorylation c-Met and SCF were up-regulated, while VCAM -1, MMP-9, SDF -1 or CXCR4 were not changed. SCF level in conditioned media was also increased after the HGF stimulation. Finally, we examined whether the bone marrow stem cells in PB mobilized by HGF transdifferentiate into hepatocytes. Using GFP-chimera-mice given acute liver injury after administration of retorolusine and CCl4, the levels of GFP+ cells in liver of GFP-chimera-mice 2 months after treatment by PBS and HGF were 2.2±1.4% and 12.7±3.6%, respectively (p<0.01). In conclusion, HGF can mobilize stem cells with long-term engraftment capabilities from bone marrow to peripheral blood, resulting in contribution to liver regeneration.

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