Effect Of CD34 Research Articles

The effect of CD 34+ stem cell dose on both short-term and long-term outcomes of autologous stem cell transplantation in multiple myeloma

The effect of CD 34+ stem cell dose on both short-term and long-term outcomes of autologous stem cell transplantation in multiple myeloma

Effect of CD34⁺ Total/Myeloid CD34⁺ Cell Progenitors and B-Lymphoid Progenitors Within the Bone Marrow Grafts on the Hematopoietic Recovery After Hematopoietic Stem Cell Transplantation.

The influence of CD34⁺ cells on transplant outcomes following hematopoietic stem cell transplantation remains controversial. A minimum of 2.0 to 2.5 million CD34⁺ cells/kg of patient weight is requested for a rapid and durable engraftment. The aim of this study was to detect the ratio of CD34+ B-lymphoid progenitors (hematogones) in bone marrow grafts and investigate their effects on hematopoietic recovery after transplant. Our study included 41 patients who received a bone marrow graft from their HLA-matched donor from 2016 through 2019. The CD34⁺ cell numbers within the graft were detected using Stem-Kit (Beckman Coulter). The ratio of CD34⁺ hematogones was determined either by their light scatter characteristics or by the detection of CD34, CD19, or CD10 coexpressing cells in a separate tube. The median number of CD34⁺ cells was 5.9 × 106/kg (0.8-14.3 × 106/kg). The CD34⁺ cells consisted of 71% (range, 35.7%-100%) and 29% (range, 5.7%-64.3%) myeloid and B-lymphoid progenitors, respectively. Percentage of CD34⁺ (P < .001) and total (P < .001) hematogones in correlation with donor age. Time of neutrophil engraftment was significantly longer (P = .039) when total infused CD34⁺ cell content was <3 × 106/kg. A remarkable population of hematogones within the CD34⁺ cell pool was detected in bone marrow grafts. Detection of the ratio of hematogones and most primitive stem cells (CD34⁺CD90⁺CD38⁻) may overall provide more information to build a better correlation between CD34⁺ cell content and the recovery of bone marrow.

Effect of CD34+ cell dose on neutrophil and platelet engraftment kinetics in haematopoietic stem cell transplantation – A single-centre experience

Objectives: Haematopoietic stem cell transplantation (SCT) is curative for a number of benign and malignant hematological disorders. CD34 expression on haematopoietic progenitor cells is used to assess stem cell content in peripheral blood stem cell and bone marrow grafts. This study evaluated the relationship between numbers of CD34+ cells infused per kg and the timing of neutrophil and platelet engraftment. Materials and Methods: The effect of cell dose was studied in consecutive HSCT patients transplanted between November 2008 and December 2017. Neutrophil engraftment was defined as the first of 2 consecutive days with an absolute neutrophil count &gt;0.5 × 109/L and platelet engraftment as unsupported platelet count &gt;20 × 109/L for 7 days. Results: Of a total of 131 patients, 26 (19.8%) underwent an autologous SCT, while 105 (80.2%) underwent an allogeneic SCT. The median CD34 dose infused in the auto-SCT group was 5.29 × 106 CD34+cells/kg (IQR = 2.95–10.98) and 6.42 × 106 CD34+cells/kg (IQR = 4.20–9.20) in the allo-SCT group (P = 0.773). The median time to neutrophil engraftment in the auto-SCT group was 11 days (range 9.5–12) and in the allo-SCT group was 15 days (range 13–17), P ≤ 0.001. The median time to platelet engraftment in both groups was similar (12 days). When patients were divided into three groups based on CD34 dose (&lt;5, 5–8 and &gt;8), no difference was observed in the time to ANC or platelet engraftment. Similarly, no differences in time to engraftment were noted in each quartile of CD34 dosage in auto- and allo-SCT. Conclusion: Thus, it was concluded that a cell dose of approximately 5 × 106/kg provides reasonably rapid engraftment, with no advantage seen for a higher cell dose of &gt;5.

The CD34+ Cell Dose Matters in Hematopoietic Stem Cell Transplantation with Peripheral Blood Stem Cells from Sibling Donors

The effect of CD34+ cell dose in allogeneic hematopoietic stem cell transplantation (HSCT) on overall survival (OS) and incidence of acute and chronic graft-versus-host disease (GvHD) has not been established and few studies have been performed. Our single center analysis included 189 patients with hematological malignancies who received peripheral blood stem cell (PBSC) grafts from sibling donors. Myeloablative conditioning was used in 88 cases and 101 received reduced intensity conditioning. The median CD34+ cell dose was 5.6 × 106/kg (0.6–17.0). In the multivariate analysis, a CD34 cell dose of 6–7 × 106/kg was associated with better OS and lower transplant-related mortality (TRM), while a dose of <5 × 106/kg led to increased relapse and reduced chronic GVHD (cGVHD). A high CD34 cell-dose (>6.5 × 106/kg) correlated with less acute GVHD (aGVHD) II–IV. We conclude that the CD34 cell dose has an impact on the outcome of HSCT from sibling donor PBSCs.

The CD34+ Cell Dose Matters in Hematopoietic Stem Cell Transplantation with Sibling Donors Receiving Peripheral Blood Stem-Cells

Background The outcome of allogeneic hematopoietic stem cell transplantation (HSCT) is influenced by many factors (underlying disease, HLA-matching, patient and donor age, CMV serostatus, co-morbidities, conditioning regimen, GVHD prophylaxis and graft source and composition). The number of T-cells contained in the graft is associated with the incidence and severity of GvHD. The effect of CD34+ cell dose in HSCT on overall survival and incidence of acute and chronic GvHD is less well established. Patients & Methods We analyzed transplant outcomes in 189 patients with hematological malignancy and sibling donor receiving G-CSF mobilized peripheral blood stem cell grafts. Myeloablative conditioning was given to 88 patients and reduced intensity conditioning to 101 patients. Median CD34+ cell dose was 5.6 × 106/kg (0.6-17.0). Anti-thymocyte globulin (ATG) was not given. Results Median time to neutrophil engraftment (ANC >0.5 × 109/L) was 17 days. In multivariate analysis The 5-year overall survival (OS) for all patients was 47%. The best 5-year OS (71%) was seen in patients receiving 6-7 × 106CD34+cells/kg (HR: 0.43, 95% CI: 0.24-0.78, p=0.005) (fig 1). Transplant related mortality at 1 and 5 years was 19% and 28%, respectively. The lowest TRM (15%) was found among patients given a CD34+ cell dose of 6-7 × 106cells/kg (HR: 0.41, 95% CI: 0.18-0.92, p=0.03). The cumulative incidence of relapse (RI) for all patients was 29%. Increased RI (41%) was found in patients who received In total, 86 (46%) and 92 (56%) patients developed acute and chronic GvHD, respectively. The cumulative incidence of acute GVHD grades II-IV in the whole cohort was 40%. The lowest incidence (33%) of aGVHD II-IV was found among patients receiving a high cell-dose. In the corrected multivariate analysis, a CD34+ cell dose of >6.5 × 106cells/kg was associated with a lower incidence of aGVHD II-IV (RH: 0. 53, 95% CI: 0.29-0.97, p=0.04). In the corrected multivariate analysis a CD34 cell dose of 6-7 × 106/kg was associated with better OS and lower TRM, while a CD34 cell-dose of 7 × 106/kg) correlated to less aGVHD II-IV. Conclusion The CD34 cell dose has impact on the outcome in sibling donor HSCT using peripheral-blood stem-cells.

The Impact of Biomarkers in Predicting the Response to CD34+ Cell Therapy in Non-Ischemic Dilated Cardiomyopathy Patients

Purpose Although data on beneficial effects of CD34+ therapy in non-ischemic dilated cardiomyopathy (DCM) is accumulating, the individual patient response is highly variable. We sought to investigate the role of biomarkers in predicting clinical response to transendocardial CD34+ cell transplantation in DCM patients. Methods We enrolled 37 DCM patients (NYHA class III, LVEF 5%. At the time of CD34+ cell transplantation we performed analysis of 8 biomarkers of angiogenesis (angiopoietin-1, FGF-acidic, FGF-basic, PDGF-AA, PDGF-BB, VEGFA, VEGFD, angiogenin). Results Of 37 patients, 26 (70%) responded to CD34+ cell therapy (responders), and 11 (30%) were classified as non-responders. The groups did not differ in age (56±14 years in responders vs. 59±11 years in non-responders, P=0.43), gender (male: 85% vs. 78%, P=0.36) and baseline LVEF (31±8% vs. 32±6%, P=0.69). When compared to non-responders, responders had lower levels of NT-proBNP (1159±1043 ng/L in responders vs. 2667±2252 ng/L in non-responders, P=0.005), lower scar burden (47±17% vs. 58±15%, P=0.003), lower levels of VEGFA (57± 8 ng/mL vs. 85±18 ng/mL, P=0.001) and higher levels of angiopoietin-1 (1.6±0.9 ng/mL vs. 1.2±0.3 ng/mL, P=0.006). Significant correlation was also found between these two biomarkers of angiogenesis and scar burden (VEGFA: P=0.039, r=0.60, angiopoietin-1: P=0.04, r=0.45). Conclusion Lower levels of angiopoietin-1 and higher levels of VEGFA correlate with higher scar burden and poor clinical response in DCM patients undergoing transendocardial CD34+ cell transplantation. Thus, these biomarkers could represent a non-invasive tool for predicting response to CD34+ cell therapy.

Pre-Treatment with Bendamustine Does Not Affect Stem Cell Mobilization in Patients with Indolent Non-Hodgkin Lymphomas: A Multicenter Study on Behalf of the Fondazione Italiana Linfomi

Bendamustine (B) is an alkylating agent with unique chemical structure (purine-like benzimidazole ring) and high cytotoxic activity. In the last decade, the association of B and rituximab (BR) emerged as the worldwide most popular standard treatment of patients (pts) with indolent non-Hodgkin lymphomas (iNHL), in both relapsed/refractory (R/R) and untreated setting. Autologous stem-cell transplant (ASCT) is the standard option in young fit pts with R/R iNHL and has been recently demonstrated to improve survival of follicular lymphoma (FL) pts with early treatment failure (ETF: within 2 years [yrs] of frontline immunochemotherapy [I-CT], Casulo et al, BBMT 2018). The structure similarity with fludarabine, which is associated with a well-known peripheral blood stem cell (PBSC) mobilization impairment, may limit the use of B in younger pts with iNHL potentially candidates for ASCT. Moreover, the effectiveness of CD34+ cells collection in pts treated previously with B is essentially still unknown and based on few small series.We retrospectively analyzed rates of CD34+ cells collection in consecutive pts with iNHL undergoing PBSC mobilization attempt, who had previously received treatment with B (in the same or in a previous line of therapy) in 12 centers of the Fondazione Italiana Linfomi. The primary endpoint was the rate of pts who were able to obtain a successful harvest of PBSC (≥2 x106/Kg of body weight).Overall, we collected complete data about 45 pts with iNHL undergoing PBSC mobilization attempt after previous treatment with B (Table 1). The majority of pts had FL (n=39). Median age at diagnosis was 52 yrs (35-66). Frontline treatments comprised R-CHOP in 27 pts (60%) and BR in 11 (24%). All but 2 pts, who were mobilized during 1st line therapy, experienced disease relapse and initiated 2nd line treatment, including reinduction I-CT, PBSC mobilization and ASCT consolidation. Among pts with FL, 13 (33%) relapsed within 24 months (ETF). Median lines of therapy at PBSC mobilization were 2 (1-4). Eleven pts (24%) received B in 1st line, 29 (65%) as part of 2nd line (n=29, 65%), and 5 (11%) in 3rd or 4th line of therapy. The most frequent mobilization strategy (40 cases, 88%) was CT plus G-CSF (including R-HD-AraC in 27), with “on demand” plerixafor adjunction in 4 cases (10%). Then, two pts (4%) underwent PBSC mobilization with G-CSF only (+ plerixafor in 1) while 3 pts (7%) received G-CSF (+ plerixafor in 1) immediately after a BR course. At first mobilization attempt, 38 out of 45 pts (84%) collected ≥2 x106 CD34+/Kg (Table 2), including 2/2 (100%) in G-CSF only, 35/40 (88%) in CT + G-CSF and 1/3 (33%) in BR cohort (p=0.039), with a median of 1 (1-4) apheresis procedure. Five out of 7 pts who failed first mobilization underwent a second attempt (1 with G-CSF + plerixafor, 3 with CT + G-CSF and 1 with CT + G-CSF + plerixafor) collecting all ≥2 x106 CD34+/Kg. Considering all mobilization attempts, 43/45 pts (96%) reached successful harvest of PBSC (≥2 x106/Kg) and 38/45 (84%) obtained an optimal PBSC collection (≥5 x106/Kg). Median number of PBSC collected was 6.46 x106/kg (3-18). Pre-mobilization bone marrow involvement significantly affected PBSC mobilization (p=0.03), as well as response at mobilization (CR 92%, PR 60%, SD 50%, p=0.02) while cumulative dose of B (>720 mg/m2, p=0.9) or timing from last B administration (≤3 months, p=0.34) did not. At multivariable analysis, mobilization type (p<001) and response at mobilization (p=0.02) retained independent significance, while BM involvement did not (p=0.07). Overall, 30 out of 43 pts who efficiently mobilized PBSC (70%) finally underwent ASCT, with complete and fast engraftment (median time to ANC>500/μl and PLT >20000/μl: 11 and 13 days). We observed 1 case of MDS (EB-2) and 1 sarcoma after ASCT. At a median follow-up of 6.3 yrs (0.7-14), only 3 pts died (2 for progression and 1 for viral encephalitis), with 8-yrs OS of 89.6% (Fig. 1) and a median PFS from ASCT of 8.1 yrs. Notably, FL pts experiencing ETF did not exhibit worse OS (85.7 vs 87.1% at 8-yrs, p=0.7).High rate of success in PBSC collection reported in this large real-world study supports the evidence that pre-treatment with B does not affect PBSC mobilization in iNHL pts, although we confirmed that B does not display per se a mobilizing capacity. Salvage strategy including ASCT resulted in overall favorable outcome in young pts with R/R iNHL and seemed able to overcome the negative prognostic impact of ETF in FL. [Display omitted] DisclosuresLuminari:Celgene: Consultancy; Roche: Consultancy; Gilead: Consultancy; Servier: Consultancy; Sandoz: Consultancy. Passamonti:Celgene: Consultancy, Speakers Bureau; Roche: Consultancy; Novartis: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Speakers Bureau.

Effects of CD34(+) selected stem cells for the treatment of poor graft function after allogeneic stem cell transplantation

目的观察输注纯化供者CD34+细胞治疗单倍型造血干细胞移植后移植物功能不良的疗效和安全性。方法对2014年1月至2018年3月期间接受供者纯化CD34+细胞治疗的12例单倍型造血干细胞移植后移植物功能不良患者进行回顾性分析。结果12例患者中男9例、女3例，中位年龄26（14~54）岁；急性淋巴细胞白血病4例，急性髓系白血病5例，慢性髓性白血病2例，慢性粒-单核细胞白血病1例。分选产物CD34+细胞纯度为92.0%（44.0%~97.0%），回收率为55.0%（45.0%~96.7%），回输CD34+细胞的中位数为1.9（0.9~4.4）×106/kg，CD3+细胞中位数为0.6（0.3~2.0）×104/kg。中性粒细胞恢复中位时间为18（14~39）d，血小板恢复中位时间为29（16~153）d，红细胞恢复中位时间为60（9~124）d。12例患者输注过程中未发生严重不良反应，10例获得完全缓解，1例患者获得部分缓解，1例患者无效，未发生重症感染和重度GVHD。结论回输供者纯化CD34+细胞是单倍型造血干细胞移植后植入功能不良的一种安全、有效治疗方法。

Slit2 Modulates the Inflammatory Phenotype of Orbit-Infiltrating Fibrocytes in Graves' Disease.

Human CD34+ fibrocytes, circulating monocyte lineage progenitor cells, have recently been implicated in thyroid-associated ophthalmopathy (TAO), the ocular manifestation of Graves' disease (GD). Fibrocytes express constitutive MHC class II (MHC-2) and, surprisingly, thyroglobulin (Tg) and functional thyrotropin (TSH) receptor (TSHR). Underlying expression of these thyroid proteins is the autoimmune regulator protein (AIRE). Fibrocytes respond robustly to TSH and thyroid-stimulating Igs by generating extremely high levels of inflammatory cytokines, such as IL-6. In TAO, they appear to infiltrate the orbit, where they transition to CD34+ orbital fibroblasts (OF). There, they coexist with CD34- OF as a mixed fibroblast population (GD-OF). In contrast to fibrocytes, GD-OF express vanishingly low levels of MHC-2, Tg, TSHR, and AIRE. Further, the amplitude of IL-6 induction by TSH in GD-OF is substantially lower. The molecular basis for this divergence between fibrocytes and CD34+ OF remains uncertain. In this article, we report that Slit2, an axon guidance glycoprotein, is constitutively expressed by the CD34- OF subset of GD-OF. Culture conditioned medium (CM) generated by incubating with GD-OF and CD34- OF substantially reduces levels of MHC-2, Tg, TSHR, and AIRE in fibrocytes. Expression can be restored by specifically depleting CM of Slit2. The effects of CD34- OF CM are mimicked by recombinant human Slit2. TSH induces Slit2 levels in GD-OF by enhancing both Slit2 gene transcription and mRNA stability. These findings suggest that Slit2 represents a TSH-inducible factor within the TAO orbit that can modulate the inflammatory phenotype of CD34+ OF and therefore may determine the activity and severity of the disease.

(473) - The Effects of CD34+ Cell Therapy in Heart Failure with Preserved Ejection Fraction

(473) - The Effects of CD34+ Cell Therapy in Heart Failure with Preserved Ejection Fraction

Effects of Transendocardial CD34+ Cell Transplantation on Diastolic Parameters in Patients with Nonischemic Dilated Cardiomyopathy

We sought to evaluate the physiological background and the effects of CD34+ cell transplantation on diastolic parameters in nonischemic dilated cardiomyopathy patients (DCM). We enrolled 38 DCM patients with NYHA class III and LVEF < 40% who underwent transendocardial CD34+ cell transplantation. Peripheral blood CD34+ cells were mobilized by G‐CSF, collected via apheresis, and injected transendocardially in the areas of myocardial hibernation. Patients were followed for 1 year. At baseline, estimated filling pressures were significantly elevated (E/e′ ≥ 15) in 18 patients (Group A), and moderately elevated (E/e ′< 15) in 20 patients (Group B). The groups did not differ in age (54 ± 9 years vs. 52 ± 10 years; p = .62), gender (male: 85% vs. 78%; p = .57), or LVEF (31 ± 7% vs. 34 ± 6%; p = .37). When compared to Group B patients in Group A had more segments with myocardial scar (4.9 ± 2.7 vs. 2.7 ± 2.9; p = .03), myocardial hibernation (2.2 ± 1.6 vs. 0.9 ± 1.1; p = .02), and longer average local relaxation time on electroanatomical mapping (378 ± 41 ms vs. 333 ± 34 ms, p = .01). During follow‐up there was an improvement in diastolic parameters in Group A (E/e′: from 24.3 ± 12.1 to 16.3 ± 8.0; p = .005), but not in Group B (E/e′: from 10.2 ± 3.7 to 13.2 ± 9.1; p = .19). Accordingly, in Group A, we found an increase in 6‐minute walk distance (from 463 ± 83 m to 546 ± 91 m; p = .03), and a decrease in NT‐proBNP (from 2140 ± 1743 pg/ml to 863 ± 836 pg/ml; p = .02). In nonischemic DCM, diastolic dysfunction appears to correlate with areas of myocardial scar and hibernation. Transendocardial CD34+ cell transplantation may improve diastolic parameters in this patient cohort. Stem Cells Translational Medicine 2017;6:1515–1521

Comparison between the Effect of CD34+ Stem Cells and Mesenchymal Stem Cells in Improving Pulmonary Fibrosis in Bleomycin Rat Model

Comparison between the Effect of CD34+ Stem Cells and Mesenchymal Stem Cells in Improving Pulmonary Fibrosis in Bleomycin Rat Model

Abstract 15453: CD34+ Cell Therapy May Affect Extracellular Matrix Turnover in Patients With Non-ischemic Dilated Cardiomyopathy

Introduction: The underlying mechanisms of CD34+ cell therapy in patients with non-ischemic dilated cardiomyopathy (DCM) remain poorly defined Hypothesis: We sought to evaluate the effects of CD34+ cell therapy on extracellular matrix. Methods: We performed a cohort analysis of 23 consecutive patients with DCM who underwent transendocardial CD34+ cell transplantation between January and December 2013. All patients received 5-day stimulation with G-CSF; CD34+ cells were selected with apheresis and injected transendocardially guided by electroantomical mapping. Patients were followed for 6 months and good clinical response was defined as an increase of left ventricular ejection fraction (LVEF) ≥5%. Extracellular matrix turnover was evaluated by measuring changes in galectin-3 serum levels. Results: Within 6 months after cell therapy galectin-3 levels decreased in 9 (39%) patients (Group A) and increased in 14 (61%, Group B). The two groups did not differ with regards to gender (male: 100% in Group A vs. 78% in Group B; P=0.15), age (51±10 years vs. 52±11 years; P=0.79), serum creatinine (86±22 μmol/L vs. 82±17 μmol/L, P=0.62), bilirubine (20±11 μmol/L vs. 17±9 μmol/L, P=0.51), or NT-proBNP levels (1465±1448 pg/mL vs. 1380±1626 pg/mL, P=0.72). Baseline LVEF (28±9% vs. 33±7%, P=0.10) and left ventricular end-diastolic diameter (7.1±0.8 cm vs. 6.5±0.7 cm, P=0.22) were also comparable in the two groups. Both groups received comparable doses of CD34+ cells (84±51 million cells in Group A vs. 132±96 million cells in Group B, P=0.21). At 6 months LVEF increased significantly more in Group A than in Group B (9.2±5.1% vs. 3.4±5.2%, P=0.01) and the same was true for 6-minute walk test distance (83±47 m vs. 37±27 m, P=0.03). NT-proBNP decreased in Group A (-356±684 pg/mL), but not in Group B (+449±1040 pg/mL, P=0.07) and overall clinical response was significantly better in Group A than in Group B (responders: 88% vs. 33%, P=0.008). Conclusions: In non-ischemic DCM, clinical response to CD34+ cell therapy appears to correlate with changes in galectin-3 serum levels. This suggests that the effects of CD34+ cell therapy may be partially mediated through remodelling of the extracellular matrix.

Clinical Effects of CD34+ Cell Transplantation in Non-Ischemic Dilated Cardiomyopathy Correlate with Myocardial Cell Engraftment

Purpose In pre-clinical models of stem cell therapy, early myocardial cell engraftment predicted late cardiac functional recovery. We sought to analyze the effect of myocardial homing of CD34 + cells on clinical outcome in patients with non-ischemic dilated cardiomyopathy (DCM). Methods and Materials In 94 patients with non-ischemic DCM, stem cells were mobilized by daily subcutaneous injections of filgrastim. CD34 + cells were collected via apheresis and labeled with technetium. Cells were injected intracoronary in the artery supplying segments of reduced myocardial viability (n=53), or transendocardially in the target areas defined by electro-anatomical mapping (n=41). Nuclear imaging for quantitation of myocardial homing was performed 18 hours after the procedure.Good homing was predefined as measured activity greater than median value of general activity.Patients were followed for 1 year. Results At baseline, patients with good (>median, group A) and poor (≤median, group B) homing did not differ in age, gender, LVEF, or plasma levels of creatinine or NT-proBNP. The number of mobilized CD34 + cells used for injection was comparable in both groups (98±56 x 10 6 in group A vs. 101±38 x 10 6 in group B, P=0.73). Transendocardial cell injection was more frequent in group A (62%) than in group B (32%, P=0.01). At year 1, LVEF improved more in group A (+6.2±2.8 %) than group B (+2.7±1.7 %, P=0.01). The same was true for 6-minute walk test distance (+101±21 m in group A vs. +46±11 m in group B, P=0.01) and levels of NT-proBNP (−733±2411 pg/ml vs. −115±123 pg/ml, P=0.006). In both groups, we found no significant change in LVEDD (-0.08±0.16 cm in group A vs. -0.06±0.10 cm in group B, P=0.70). Conclusions In patients with non-ischemic DCM, higher myocardial CD34 + cell homing is associated with superior improvement in ventricular function, NT proBNP levels, and exercise capacity. This suggests that early myocardial cell engraftment translates into long-term clinical benefit in this patient cohort.

The effect of CD34+ cell‐containing autologous platelet‐rich plasma injection on pattern hair loss: a preliminary study

Mobilized CD34+ cells in peripheral blood have angiogenic potential, which is an important factor in active hair growth. In addition, activated autologous platelet-rich plasma (PRP) has been reported to induce the proliferation of dermal papilla cells. To investigate the clinical efficacy of interfollicular injection of CD34+ cell-containing PRP preparation for pattern hair loss. CD34+ cell-containing PRP preparation was injected on the scalps of 13 patients with pattern hair loss, and 13 patients were treated with interfollicular placental extract injection as a control. The numbers of platelets in PRP were microscopically counted and CD34+ cells were evaluated with flow cytometry. Three months after the first treatment, the patients presented clinical improvement in the mean number of hairs, 20.5 ± 17.0% (P < 0.0001), mean hair thickness, 31.3 ± 30.1% (P < 0.0001), and mean two-point score, 84.4 ± 51.7% (P < 0.0001) compared with baseline values. At 6 months, the patients presented clinical improvement in mean hair count, 29.2 ± 17.8% (P < 0.0001), mean hair thickness, 46.4 ± 37.5% (P < 0.0001), and mean two-point score, 121.3 ± 66.8% (P < 0.0001) compared with baseline. The MIXED procedure revealed that CD34+ cell-containing PRP treatment presented a higher degree of improvement than placental extract treatment in hair thickness (P = 0.027) and overall clinical improvement (P = 0.023). Our data suggest that the interfollicular injection of autologous CD34+ cell-containing PRP preparation has a positive therapeutic effect on male and female pattern hair loss without remarkable major side-effects.

CD34 + cell infusion after ST elevation myocardial infarction is associated with improved perfusion and is dose dependent

the objective of the study was to determine whether the effects of infarct-related artery (IRA) infusion of autologous bone marrow-derived CD34(+) cells after ST elevation myocardial infarction (STEMI) are dependent on the dose (quantity and mobility) of the cells infused. Beneficial effects of IRA infusion of mononuclear cells after STEMI have been inconsistent, possibly because of differences in timing, cell type, quantity, and mobility of infused cells. patients were randomized to bone marrow harvest (n = 16) or control (n = 15). At a median of 8.3 days after coronary stenting for STEMI, CD34(+) cells were infused via the IRA at 3 dose levels (5, 10, and 15 × 10(6)) in cohorts of 5 patients each. Baseline and follow-up imaging and ex vivo CD34(+) cell mobility were performed. Cell harvest and infusion were safe. Quantitative rest hypoperfusion score measured by single-photon emission computed tomography improved at 6 months in the ≥ 10 million cohorts compared with controls (-256 vs +14, P = .02). There was a trend toward improved ejection fraction at 6 months (+4.5%) in the ≥ 10 million cohorts compared with no change in the controls and 5 million cohort (+0.7%). Improved perfusion and infarct size reduction correlated with the quantity and mobility of the infused CD34(+) cells. the effects of CD34(+) cell IRA infusion during the repair phase after STEMI are dose dependent and, at a threshold dose of 10 million CD34(+) cells, associated with a significant improvement in perfusion that may limit deterioration in cardiac function (IRA infusion of CD34(+) cells in patients with acute myocardial infarction [AMR-01] NCT00313339).

Effect of CD34+ Stem Cell Injection and their Mobilization from Bone Marrow by Granulocyte-Colony Stimulating Factor in Regeneration of Myocardium after Experimental Induction of Acute Myocardial Infarction in Adult Albino Rat

Objective: the aim of the study is to investigate the histological, biochemical and the immunohistochemical effects of both intravenous injection of cord blood dervied-stem cell CD34+, and their mobilization from bone marrow by subcutaneous injection of granulocyte colony-stimulating factor (GC-SF) after induction of acute myocardial ischemia. Materials and Methods: the study included 4 groups of albino rats (8 rats each). The first was reserved as control, while the other 3 groups were subjected to induction of acute myocardial ischemia. The second one was considered as ischemic group without any treatment. The third received intravenous cord blood injection after induction of ischemia. The myocardium were dissected and stained with H & E and Masson trichrome (for histological studies), and immunoperoxidase (for immunohistochemical studies). Results: there was a decrease in the extent of myocarial fibrosis in groups treated with GC-SF, and a significant decrease in those treated with cord blood stem cells. A Parallel to the significant increase in the number of positively stained vascular endothelial cells in rats treated with cord blood stem cells was detected. Conclusion: cord blood derived-stem cell CD34+ and GC-SF depressed myocaridal ischemia; however, further studies are needed to know the mechanism of regeneration of teh myocardium after its damage.

Platelet Engraftment in Patients with Hematologic Malignancies following Unmanipulated Haploidentical Blood and Marrow Transplantation: Effects of CD34 + Cell Dose and Disease Status

Unmanipulated haploidentical blood and marrow transplantation has been developed as an alternative transplantation strategy for patients without an HLA-matched related or unrelated donor. In this transplantation setting, factors associated with hematopoietic recovery have not been defined completely. The aim of this study was to investigate the effects of donor and recipient characteristics on neutrophil and platelet engraftment after unmanipulated HSCT. The study group comprised 348 patients who underwent unmanipulated haploidentical blood and marrow transplantation to treat hematologic malignancy at a single institution between 2002 and 2007. Factors correlating with neutrophil and platelet engraftment posttransplantation were analyzed retrospectively. All patients achieved an absolute neutrophil count ANC of 500/μL in a median of 13 days (range, 9 to 49 days). Of the 348 patients, 331 (95.11%) achieved an untransfused platelet count of > 20,000/μL in a median of 16 days (range, 7 to 356 days). Multivariate analysis showed that the amount of CD34 + cells infused (CD34 + cells ≥ 2.19 × 10 6/kg recipient weight vs < 2.19 ×10 6/kg recipient weight; hazard ratio [HR] = 1.695; 95% confidence interval [CI] = 1.361 to 2.112; P < .0001), and disease stage (advanced vs early; HR = 0.724; 95% CI = 0.577 to 0.907; P = .005) were independently associated with increased risk of platelet engraftment. Our results suggest that low numbers of CD34 + cells in allografts and advanced-stage disease may be critical factors associated with delayed platelet engraftment after unmanipulated haploidentical transplantation.

Effect of CD34+ cell dose on hematopoietic reconstitution and outcome in 508 patients with multiple myeloma undergoing autologous peripheral blood stem cell transplantation

We analyzed the hematopoietic reconstitution and outcome of 508 patients with multiple myeloma (MM) with respect to the number of CD34+ cells reinfused at our center. Each cohort of 390 patients (unselected CD34+ cell transplant) and 118 patients (CD34+ selected transplant) was divided into four subgroups. Among the 390 transplantations, 86 patients received a high dose (HD-) of > or =6.50 x 10(6) unselected CD34+ cells/kg, 116 patients a low dose (LD-) of <3.00 x 10(6) CD34+ cells/kg. Among the patients treated with CD34+ selected PBSC, 34 received > or =6.50 x 10(6) CD34+ cells/kg (HD+) and 16 <3.00 x 10(6) CD34+ cells/kg (LD+). HD- patients experienced a reduced median time to leukocyte (13 d vs. 14 d) (P < 0.001) and platelet reconstitution >20 x 10(9)/L (10 d vs. 12 d) (P < 0.001). Similarly, HD+ showed a reduced median time to leukocyte (12 d vs. 15 d) (P < 0.001) and platelet recovery >20 x 10(9)/L (10 d vs. 11 d) (P = 0.058). CD34+ cell-dose was significant for long-term platelet recovery at day 360 (unselected transplant P = 0.015, selected transplant P = 0.023). Number of transplanted CD34+ cells had no significant impact on transplant related mortality, overall survival or CR/PR rates within 100 d. In terms of supportive care the differences of high-/low-dose grafts were minimal. These results confirm that high doses of CD34+ PBSC shorten hematopoietic reconstitution and reduce hospitalization. Nevertheless secure engraftment results from transplantation of 2.00-3.00 x 10(6) CD34+ cells/kg. As 60% of our pretreated patients are able to collect > or =5.00 x 10(6) CD34+ cells/kg within a single leukapheresis, division into two or more freezing bags allows safe tandem transplantation in the majority of MM patients.

Cardiotropic effect of extracardiac transplantation of embryonic human myoblasts to mice with bradycardia: Various effects of cell material

Animals with bradycardia were detected in reproductive colony of mdx mice. Low pulse rate was associated with poor survival and predisposition to sudden death, but did not directly depend on the presence of dystrophin mutant gene or animal age. Heart rate increased in old mice with bradycardia after extracardial, intramuscular, and intravenous injection of human embryonic myoblasts. Stable normalization of the pulse was observed 2 weeks after transplantation, but early peak of heart rate was observed as early as 24 h after cell transplantation. Cell suspensions, which could contain stem cells (blood mononuclears and CD34+ lymphocytes), also corrected heart rhythm. Unlike the effect of myoblasts, cardiotropic effect of mononuclears was preceded by a period of tachycardia, while the effect of CD34+ lymphocytes was very unstable. The cardiotropic effect of myoblasts was combined with life span prolongation and certain rejuvenation in some animals. Erythrocytes and supernatant obtained during blood cell fractionation did not modify the heart rhythm in mice with bradycardia. After injection of myoblasts to mice with rare and normal pulses serum creatine kinase activity decreased with different rates. These data attest to a variety of biological effects of stem cells and/or their derivatives and to ambiguous mechanisms of these effects.