Bone Marrow Transplantation Animal Models

Mehdi Bendjelloul^*
*Correspondence: Mehdi Bendjelloul, Department of Hematology and Histocompatibility, Amiens University Medical Center, Amiens, France, Email:

Keywords

Acute myeloid leukemia • Chimerism • Hematopoietic stem‐cell transplantation

Introduction

The United States and the European Union share a common approach regarding which products require marketing authorization to be "distributed" on the "market" and which do not in order to simplify the regulatory framework as much as possible. In the United States, the majority of minimally manipulated products that are intended for homologous use and do not combine other agents are regulated by section 361 of the Public Health Service Act, so they do not require the pre-market approval that is required for products regulated by section 351. Advanced therapy medicinal products (ATMPs) that, in the case of cells and tissue-based products, are primarily those that have been significantly manipulated or that are not intended to be used for the same essential function(s) in the recipient as in the donor must undergo a centralized procedure to obtain marketing approval in the EU [1].

Description

Mesenchymal stem cells (MSC) derived from adult bone marrow can differentiate into a variety of lineages. They are positive for CD29, CD44, CD105 and CD166, have a two-day doubling time, can grow sixfold in culture and some of the cytokine receptors these cells express and the cytokines they produce remain unchanged in their biological functions. Comparable cells isolated from fetal blood, liver and bone during the first and second trimesters, from amniotic fluid and umbilical cord blood and from adult peripheral blood, compact bone and adipose tissue share many of their characteristics and properties. In addition, a CD133-positive subpopulation of these cells has demonstrated the ability to differentiate into endothelium and cells with neuroectodermal phenotype and function in addition to mesenchymal cell types (osteoblasts, chondrocytes, adipocytes and myocytes) during more than one hundred population doublings under defined conditions. Previously, it was thought that adult marrow-derived stem cells could only produce a limited number of different kinds of cells, whereas embryonic cells were totipotent [2]. The gap has clearly shrunk since these adult multipotent stem cells were discovered: For the treatment of inherited or degenerative diseases as well as the repair of tissues like cartilage, bone and myocardium, they present a very promising and much more abundant potential resource.

The chimerism assay is used to monitor cell engraftment and quantify the proportions of donor and recipient cells in blood or bone marrow samples following allogeneic hematopoietic stem cell transplantation (alloHSCT). Within the first six months after alloHSCT, we wanted to better assess the value of determining CD3+ cell chimerism. This study included 145 patients who had been diagnosed with acute myeloid leukemia. At Day 30, Day 90 and Day 120 after alloHSCT, we observed significantly lower overall survival and relapse-free survival (95%, 98%, 99%) in whole blood than in patients with full donor chimerism. When evaluating specific CD3+ cells, this result was not observed. However, patients with discordant whole blood versus selected CD3+ cell chimerism demonstrated significantly lower overall survival and relapse-free survival at Day 90, indicating the need to investigate selected cell chimerism [3].

Cytokines engaged with the clonal extension and genealogy limitation of stem/begetter cells in the haematopoietic framework might assume a significant undifferentiated from part in the creating sensory system. Tyrosine hydroxylase, a dopaminergic marker, can be induced to express itself, for instance, by interleukin-1. Additionally, in a study. Combining other mitogens with leukemia inhibitory factor, a member of the interleukin-6 cytokine family, was found to increase the proliferation of human forebrain neural stem cells [4]. Importantly, we need to think about the possibility that stem cells from the bone marrow can redifferentiate. There is already evidence that neural stem cells can differentiate into bone marrow-like cells: They were shown to be able to rebuild the haematopoietic systems of mice whose marrow had been removed. These studies suggest that the environments to which multipotent cells are exposed have an effect on the lineage path they take.

Mesenchymal stem cells in the bone marrow play a crucial role in immunomodulation and tolerance induction during allogeneic transplantation. B-cell lymphopoiesis is negatively impacted by MSC and T-lymphocyte proliferation is suppressed by cellular or non-specific mitogenic stimuli. MSC transplants that are allogeneic or xenogeneic engraft immunocompromised sheep and non-human primates. Only grade I graft-versus-host disease (GvHD) was observed when a patient was treated following myeloablation with both cultured MSC from a mismatched donor and haematopoietic stem cells. The rapid haematopoietic recovery of breast cancer patients who received autologous blood stem cells in addition to culture-expanded MSC following high-dose chemotherapy is evidence that MSC can not only reduce GvHD but also facilitate haematopoietic engraftment. MSC transplantation went well in both clinical trials [5].

Conclusion

This is the first human randomized trial to compare fractionated versus bulk HPC infusion in allotransplant recipients. In the context of allogeneic HCT, we come to the conclusion that fractionated infusion of HPCs has no additional advantages. The current practice of bulk infusion in this setting is supported by our findings.

Acknowledgement

None.

Conflict of Interest

The author shows no conflict of interest towards this manuscript.

References

1. Giannopoulou, Eleni Z., Ramona Puff, Andreas Beyerlein and Irene von Luettichau, et al. "Effect of a single autologous cord blood infusion on beta‐cell and immune function in children with new onset type 1 diabetes: a non‐randomized, controlled trial." Pediatr Diabetes 15 (2014): 100-109.

Google Scholar, Crossref, Indexed at

2. Gu, Weiqiong, Jiong Hu, Weiqing Wang and Lirong Li, et al. "Diabetic ketoacidosis at diagnosis influences complete remission after treatment with hematopoietic stem cell transplantation in adolescents with type 1 diabetes." Diabetes Care 35 (2012): 1413-1419.

Google Scholar, Crossref, Indexed at

3. Haller, Michael J., Clive H. Wasserfall, Maigan A. Hulme and Miriam Cintron, et al. "Autologous umbilical cord blood transfusion in young children with type 1 diabetes fails to preserve C-peptide." Diabetes Care 34 (2011): 2567-2569.

Google Scholar, Crossref, Indexed at

4. Haller, Michael J., Clive H. Wasserfall, Maigan A. Hulme and Miriam Cintron, et al. "Autologous umbilical cord blood infusion followed by oral docosahexaenoic acid and vitamin D supplementation for C-peptide preservation in children with Type 1 diabetes." Bone Marrow Transplant 19 (2013): 1126-1129.

Google Scholar, Crossref, Indexed at

5. Haller, Michael J., Clive H. Wasserfall, Kieran M. McGrail and Todd M. Brusko, et al. "Autologous umbilical cord blood transfusion in very young children with type 1 diabetes." Diabetes Care 32 (2009): 2041-2046.

Google Scholar, Crossref, Indexed at