Sowing the Seeds of a Fruitful Harvest: Hematopoietic Stem Cell Mobilization

Hematopoietic stem cell transplantation is the only curative option for a number of malignant and non-malignant diseases. As the use of hematopoietic transplant has expanded, so too has the source of stem and progenitor cells. The predominate source of stem and progenitors today, particularly in settings of autologous transplantation, is mobilized peripheral blood. This review will highlight the historical advances which lead to the widespread use of peripheral blood stem cells for transplantation, with a look towards future enhancements to mobilization strategies

Hematopoietic Stem Cell Source and Storage

Hematopoietic stem cell transplantation(HSCT), has been accepted as a feasible treatment option that prolongs survival in hematological malignancies. Stem cell choice during hematopoietic stem cell transplantation can differ according to the experience of physicians, mostly treated hematological diseases in the centers or ongoing clinical trials. In this chapter we will discuss the advantages and disadvantages of three stem cell sources peripheral blood, bone marrow and umbilical cord blood

Successful treatment of subcutaneously disseminated aspergillosis with caspofungin acetate in an allogeneic peripheral blood stem cell transplantation patient.

We present a patient with acute myeloid leukaemia who developed subcutaneously disseminated aspergillosis after allogeneic peripheral stem cell transplantation (PSCT). Disseminated aspergillosis after stem cell transplantation has a high mortality despite treatment with amphotericin B or one of the azoles. Aspergillosis in our patient was refractory to amphotericin B and itraconazole but was successfully treated with caspofungin acetate

Impact of COVID-19 and Future Emerging Viruses on Hematopoietic Cell Transplantation and Other Cellular Therapies

COVID-19, where Co stands for corona, VI stands for virus, and D denotes disease, in the recent past referred to as 2019 novel coronavirus or 2019-nCoV, has impacted numerous lives and businesses, and has led to a surreal emergency state within world communities. COVID-19 and the future emergence of dangerous viruses will have strong and as yet possibly unanticipated consequences and impact on the present and future use of cellular therapies. In this commentary, we offer a dispassionate assessment of where we believe COVID-19, as well as future emerging viruses, might compromise successful cell transplantation (Fig. 1). These therapies include hematopoietic cell transplantation (HCT) using umbilical cord blood (CB), bone marrow (BM), and mobilized peripheral blood, which contain hematopoietic stem (HSC) and progenitor (HPC) cells, as well as various cellular populations involved in the emerging fields of reparative and regenerative medicine. Such cell populations include HSC, HPC, mesenchymal stem/stromal cells (MSC), and immune cells such as lymphocytes used in chimeric antigen receptor (CAR) T-cell therapies, as well as pluripotent stem cell–based therapies

Case Study in Refractory Non-Hodgkin's Lymphoma: Successful Treatment with Plerixafor

The present case study describes our experience in treating a young woman diagnosed with a relapsing case of diffuse large cell lymphoma, who was heavily pre-treated with chemotherapy and radiotherapy. Our only chance to improve her survival was by using high-dose chemotherapy, followed by peripheral stem cell rescue. Unfortunately, in this patient, collecting sufficient stem cells for bone marrow transplantation proved to be very difficult since she had already been heavily treated with chemotherapy and radiotherapy. Currently, granulocyte colony-stimulating factor (G-CSF) alone or G-CSF plus chemotherapy are the most commonly used treatments for stem cell mobilization. However, 5–30% of patients do not respond to these agents. Plerixafor is a new hematopoietic stem cell-mobilizing drug that antagonizes the binding of chemokine stromal cell-derived factor-1α to CXC chemokine receptor 4. It is indicated in combination with G-CSF to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma [Kessans et al.: Pharmacotherapy 2010;30:485–492; Jantunen: Expert Opin Biol Ther 2011;11:1241–1248]. Based on our findings, we consider plerixafor to be a very efficient and practical solution to mobilize and collect stem cells among all patients in such a situation, enabling us to proceed to autologous bone marrow transplantation and peripheral stem cell rescue in order to improve the patients’ overall survival

Peripheral-Blood Stem Cells versus Bone Marrow from Unrelated Donors

BACKGROUND Randomized trials have shown that the transplantation of filgrastim-mobilized peripheral-blood stem cells from HLA-identical siblings accelerates engraftment but increases the risks of acute and chronic graft-versus-host disease (GVHD), as compared with the transplantation of bone marrow. Some studies have also shown that peripheral-blood stem cells are associated with a decreased rate of relapse and improved survival among recipients with high-risk leukemia. METHODS We conducted a phase 3, multicenter, randomized trial of transplantation of peripheral-blood stem cells versus bone marrow from unrelated donors to compare 2-year survival probabilities with the use of an intention-to-treat analysis. Between March 2004 and September 2009, we enrolled 551 patients at 48 centers. Patients were randomly assigned in a 1:1 ratio to peripheral-blood stem-cell or bone marrow transplantation, stratified according to transplantation center and disease risk. The median follow-up of surviving patients was 36 months (interquartile range, 30 to 37). RESULTS The overall survival rate at 2 years in the peripheral-blood group was 51% (95% confidence interval [CI], 45 to 57), as compared with 46% (95% CI, 40 to 52) in the bone marrow group (P=0.29), with an absolute difference of 5 percentage points (95% CI, −3 to 14). The overall incidence of graft failure in the peripheral-blood group was 3% (95% CI, 1 to 5), versus 9% (95% CI, 6 to 13) in the bone marrow group (P=0.002). The incidence of chronic GVHD at 2 years in the peripheral-blood group was 53% (95% CI, 45 to 61), as compared with 41% (95% CI, 34 to 48) in the bone marrow group (P=0.01). There were no significant between-group differences in the incidence of acute GVHD or relapse. CONCLUSIONS We did not detect significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors. Exploratory analyses of secondary end points indicated that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of chronic GVHD. (Funded by the National Heart, Lung, and Blood Institute–National Cancer Institute and others; ClinicalTrials.gov number, NCT00075816.

Milieu-adopted in vitro and in vivo differentiation of mesenchymal tissues derived from different adult human CD34-negative progenitor cell clones

Adult mesenchymal stem cells with multilineage differentiation potentially exist in the bone marrow, but have also been isolated from the peripheral blood. The differentiation of stem cells after leaving their niches depends predominately on the local milieu and its new microenvironment, and is facilitated by soluble factors but also by the close cell-cell interaction in a three-dimensional tissue or organ system. We have isolated CD34-negative, mesenchymal stem cell lines from human bone marrow and peripheral blood and generated monoclonal cell populations after immortalization with the SV40 large T-antigen. The cultivation of those adult stem cell clones in an especially designed in vitro environment, including self-constructed glass capillaries with defined growth conditions, leads to the spontaneous establishment of pleomorphic three-dimensional cell aggregates ( spheroids) from the monoclonal cell population, which consist of cells with an osteoblast phenotype and areas of mineralization along with well-vascularized tissue areas. Modifications of the culture conditions favored areas of bone-like calcifications. After the transplantation of the at least partly mineralized human spheroids into different murine soft tissue sites but also a dorsal skinfold chamber, no further bone formation could be observed, but angiogenesis and neovessel formation prevailed instead, enabling the transplanted cells and cell aggregates to survive. This study provides evidence that even monoclonal adult human CD34-negative stem cells from the bone marrow as well as peripheral blood can potentially differentiate into different mesenchymal tissues depending on the local milieu and responding to the needs within the microenvironment. Copyright (C) 2005 S. Karger AG, Basel

Stem cell collection in unmanipulated HLA-haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor-mobilised blood and bone marrow for patients with haematologic malignancies: the impact of donor characteristics and procedural settings

Unmanipulated haploidentical/mismatched related transplantation with combined granulocyte-colony stimulating factor-mobilised peripheral blood stem cells (G-PBSCs) and granulocyte-colony stimulating factor-mobilised bone marrow (G-BM) has been developed as an alternative transplantation strategy for patients with haematologic malignancies. However, little information is available about the factors predicting the outcome of peripheral blood stem cell (PBSC) collection and bone marrow (BM) harvest in this transplantation. The effects of donor characteristics and procedure factors on CD34+ cell yield were investigated. A total of 104 related healthy donors received granulocyte-colony stimulating factor (G-CSF) followed by PBSC collection and BM harvest. Male donors had significantly higher yields compared with female donors. In multiple regression analysis for peripheral blood collection, age and flow rate were negatively correlated with cell yield, whereas body mass index, pre-aphaeresis white blood cell (WBC) and circulating immature cell (CIC) counts were positively correlated with cell yields. For BM harvest, age was negatively correlated with cell yields, whereas pre-BM collection CIC counts were positively correlated with cell yield. All donors achieved the final product of ≥6 ×106 kg−1 recipient body weight. This transplantation strategy has been shown to be a feasible approach with acceptable outcomes in stem cell collection for patients who received HLA-haploidentical/mismatched transplantation with combined G-PBSCs and G-BM. In donors with multiple high-risk characteristics for poor aphaeresis CD34+ cell yield, BM was an alternative source

Determining the Optimal Time for Peripheral Blood Stem Cell Harvest by Detecting Immature Cells using Hematology Analyzer, SE-9000[TM] IMI Channel

Background :A key to successful peripheral blood stem cell transplantation is to harvest a sufficient amount of hematopoietic stem cells. A method of quickly detecting hematopoietic stem cells in peripheral blood with simple procedures using the SE-9000TM IMI channel (TOA Medical Electronics Co., Ltd., Kobe, Japan) was developed. In this study, usefulness of determining the optimal time for peripheral blood stem cell harvest using IMI channel was investigated. Method :Seventy nine peripheral blood stem cell collections were performed from thirteen patients with hematologic malignancy and nineteen patients with solid organ malignancy. In 13 cases, G-CSF was administrered following chemotherapy. In 19 cases only G-CSF was used to mobilize the peripheral blood stem cells. The counts of leukocytes, mononuclear cells, CD34 positive cells, and IMI in peripheral blood and leukapheresis products were determined. Result :The CD34 positive cell count in harvested PBSC showed positive correlation with leukocyte cell, mononuclear cell, CD34 positive cell, and IMI in peripheral blood, with correlation coefficients of 0.48, 0.27, 0.63, 0.66, respectively. Positive correlation was presented between IMI and CD34 positive cell in peripheral blood and harvested PBSC, with a correlation coefficient, 0.83 and 0.74, respectively. Conclusion :As the SE-9000TM enables determination of the number of PBSC easily and rapidly, within approximately 85 seconds, whereas CD34 assays is expensive and needs skilled operator, the measurement of IMI positive cells is clinically useful for monitoring the peripheral blood stem cell mobilization.ope

Schwann-Spheres Derived from Injured Peripheral Nerves in Adult Mice - Their In Vitro Characterization and Therapeutic Potential

Multipotent somatic stem cells have been identified in various adult tissues. However, the stem/progenitor cells of the peripheral nerves have been isolated only from fetal tissues. Here, we isolated Schwann-cell precursors/immature Schwann cells from the injured peripheral nerves of adult mice using a floating culture technique that we call “Schwann-spheres." The Schwann-spheres were derived from de-differentiated mature Schwann cells harvested 24 hours to 6 weeks after peripheral nerve injury. They had extensive self-renewal and differentiation capabilities. They strongly expressed the immature-Schwann-cell marker p75, and differentiated only into the Schwann-cell lineage. The spheres showed enhanced myelin formation and neurite growth compared to mature Schwann cells in vitro. Mature Schwann cells have been considered a promising candidate for cell-transplantation therapies to repair the damaged nervous system, whereas these “Schwann-spheres" would provide a more potential autologous cell source for such transplantation