Past, present, and future efforts to enhance the efficacy of cord blood hematopoietic cell transplantation

Abstract

Cord blood (CB) has been used as a viable source of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) in over 35,000 clinical hematopoietic cell transplantation (HCT) efforts to treat the same variety of malignant and non-malignant disorders treated by bone marrow (BM) and mobilized peripheral blood (mPB) using HLA-matched or partially HLA-disparate related or unrelated donor cells for adult and children recipients. This review documents the beginning of this clinical effort that started in the 1980’s, the pros and cons of CB HCT compared to BM and mPB HCT, and recent experimental and clinical efforts to enhance the efficacy of CB HCT. These efforts include means for increasing HSC numbers in single CB collections, expanding functional HSCs ex vivo, and improving CB HSC homing and engraftment, all with the goal of clinical translation. Concluding remarks highlight the need for phase I/II clinical trials to test the experimental procedures that are described, either alone or in combination.

A Novel Evidence That Mannan Binding Lectin (MBL) Pathway of Complement Cascade Activation is Involved in Homing and Engraftment of Hematopoietic Stem Progenitor Cells (HSPCs)

“…Hematopoietic transplants since more than 50 years are established the most successful therapeutic application of stem cells. Hematopoietic stem/progenitor cells (HSPCs) present in harvested from a donor bone marrow (BM), mobilized peripheral blood (mPB) or umbilical cord blood (UCB) unit are infused intravenously into myeloablated patient to home and subsequently engraft and expand in recipient BM microenvironment, with aim to establish long term normal hematopoiesis [1][2][3][4].…”

Noninvasive Tracking of Hematopoietic Stem Cells in a Bone Marrow Transplant Model

“…If, in the future, we can deal with this problem and find means for additional clinical efforts, it is possible that several new procedures could be used together [34], such as hybrid equipment or imaging systems. This, however, adds additional logistical problems versus the use of one procedure alone, such as requiring multifunctional probes, smart processes, and improvement of the technical limitations of imaging equipment [77]. Therefore, there is viability to translate these experimental findings into bed-side application.…”

Heme Oxygenase 1 (HO-1) as an Inhibitor of Trafficking of Normal and Malignant Hematopoietic Stem Cells – Clinical and Translational Implications

“…It is well known that HSPCs are retained in BM niches due to interaction between the CXCR4 chemokine receptor and very late antigen 4 (VLA-4, also known as α 4 β 1 integrin) receptor, which are expressed on the surface of HSPCs [10][11][12][13][14][15][16]. Their respective ligands involved in BM retention, the α-chemokine stromal-derived growth factor 1 (SDF-1) and vascular adhesion molecule 1 (VCAM-1, also known as CD106), are expressed by cells in the BM stem cell niches (e.g., by osteoblasts and stromal fibroblasts) [10][11][12][13][14][15][16]. Harvested from PB after pharmacological mobilization, HSPCs are a convenient source of cells for hematopoietic transplantation [13,14].…”

“…Their respective ligands involved in BM retention, the α-chemokine stromal-derived growth factor 1 (SDF-1) and vascular adhesion molecule 1 (VCAM-1, also known as CD106), are expressed by cells in the BM stem cell niches (e.g., by osteoblasts and stromal fibroblasts) [10][11][12][13][14][15][16]. Harvested from PB after pharmacological mobilization, HSPCs are a convenient source of cells for hematopoietic transplantation [13,14]. We proposed a crucial role for the fifth protein component of the ComC (C5) in the mobilization of HSPCs.…”

“…We propose that mobilization of hematopoietic stem/ progenitor cells (HSPCs) occurs in response to sterile inflammation, induced in the bone marrow (BM) microenvironment after administration of pro-mobilizing drugs, such as the cytokine granulocyte colony stimulating factor (G-CSF) and AMD3100 (Plerixafor), a small-molecule antagonist of the chemokine receptor CXCR4 [10][11][12][13][14][15][16]. On the other hand, a state of sterile inflammation in BM is also induced during myeloablative conditioning for hematopoietic transplantation by chemo-and/or radiotherapy and plays a role in facilitating homing and engraftment of transplanted cells [16][17][18].…”