Regulatory Systems in Bone Marrow for Hematopoietic Stem/Progenitor Cells Mobilization and Homing

Abstract

Regulation of hematopoietic stem cell release, migration, and homing from the bone marrow (BM) and of the mobilization pathway involves a complex interaction among adhesion molecules, cytokines, proteolytic enzymes, stromal cells, and hematopoietic cells. The identification of new mechanisms that regulate the trafficking of hematopoietic stem/progenitor cells (HSPCs) cells has important implications, not only for hematopoietic transplantation but also for cell therapies in regenerative medicine for patients with acute myocardial infarction, spinal cord injury, and stroke, among others. This paper reviews the regulation mechanisms underlying the homing and mobilization of BM hematopoietic stem/progenitor cells, investigating the following issues: (a) the role of different factors, such as stromal cell derived factor-1 (SDF-1), granulocyte colony-stimulating factor (G-CSF), and vascular cell adhesion molecule-1 (VCAM-1), among other ligands; (b) the stem cell count in peripheral blood and BM and influential factors; (c) the therapeutic utilization of this phenomenon in lesions in different tissues, examining the agents involved in HSPCs mobilization, such as the different forms of G-CSF, plerixafor, and natalizumab; and (d) the effects of this mobilization on BM-derived stem/progenitor cells in clinical trials of patients with different diseases.

Cure of Insulin-Dependent Diabetes Mellitus by an Autologous Hematopoietic Stem Cell Transplantation Performed to Control Multiple Myeloma in a Patient with Chronic Renal Failure on Regular Hemodialysis

“…In comparison to the utilization of BM, the use of mobilized peripheral blood stem cells is the method of choice for the following reasons: (1) increased production of HSCs and progenitor cells, (2) shorter time period required for a satisfactory repopulation of the BM after stem cell infusion, (3) faster engraftment with more rapid recovery of neutrophils and platelets, (4) few platelet and packed red blood cell transfusions, (5) faster lymphocyte reconstitution, (6) fewer febrile reactions, (7) fewer regimenrelated morbidity and mortality with less pain and lower risk to patients, and (8) fewer technical difficulties [36,46]. The agents that are used in the peripheral blood progenitor cell mobilization include: growth factors such as G-CSF, cyclophosphamide in combination with G-CSF, and plerixafor (CXCR4, chemokine receptor type-4 inhibitor) which is used to increase the yield of stem cell collections in patients experiencing poor mobilization [47][48][49][50].…”

“…However, G-CSF is the predominant stem cell mobilizer used clinically [36]. Poor mobilization occurs in up to 25% of patients and it has the following risk factors: lymphoma or MM as the primary illness, heavily pre-treated cancer patients with chemotherapy ± radiotherapy, genetic diseases such as Fanconi anemia, poor BM reserve due to low cellularity, old age, low baseline CD34+ cell count prior to apheresis and low platelet count before mobilization [36,46]. As mobilized peripheral blood progenitor cells are the main sources for auto-HSCT, collection of adequate number these cells is a critical step in the auto-HSCT setting [47].…”

Cardiomyopathy and Cell Therapy: Ejection Fraction Improvement and Cardiac Muscle Mass Increasing, after a Year of Bone Marrow Stem Cells Transplantation, by Magnetic Resonance Image

“…Magnetic resonance imaging (MRI) is the best suited to meet such broad objective thanks to its resolution and clinical applicability [35]. The use of non-invasive imaging modalities in pre clinical cell therapy studies revealed key aspects of cell biology that will not be observed by other approaches excepted for histological analysis [36,37].…”

“…The aim of this study is to identify short-term result of cell transplantation in idiopathic dilated cardiomyopathy patients (IDC) who were treated by intracoronary transplantation of autologous bone marrow mononuclear cells (BMMC) and compare these results with the placebo (PL) group, by magnetic resonance imaging [33][34][35][36][37][38].…”

Modified Hydrogels to Enhance Cellular Therapy for AKI: A Translational Challenge

“…2,9,23 Specifically, when hematopoietic stem cells are infused intravenously to a patient who is undergoing a bone marrow transplant post myeloablation, SDF-1 levels in the bone marrow niches are sufficient to recruit these CXCR4-expressing (SDF-1 receptor) hematopoietic stem cells to the bone marrow where they engraft and differentiate. 24 In the kidney post acute injury, a "facultative stem cell niche" is temporarily expressed that mediates the augmented recruitment of administered MSCs through their expression of CXCR4, the cognate receptor for this chemokine. 2,23 However, MSCs that home to the injured kidney do not engraft or differentiate, but instead temporarily exert local anti-inflammatory and trophic actions before they leave the kidney and undergo apoptosis.…”