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Protocol for MicroRNA Transfer into Adult Bone Marrow-derived Hematopoietic Stem Cells to Enable Cell Engineering Combined with Magnetic Targeting

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New agents for mobilizing peripheral blood stem cells.

Hildegard T Greinix¹, Nina Worel

¹Medical University of Vienna, Department of Internal Medicine I, Bone Marrow Transplant Unit, Waehringer Guertel 18-20, Vienna A-1090, Austria. hildegard.greinix@meduni-wein.ac.at

Transfusion and Apheresis Science : Official Journal of the World Apheresis Association : Official Journal of the European Society for Haemapheresis

|July 21, 2009

Summary

Hematopoietic stem cell (HSC) mobilization using AMD3100, a CXCR4 antagonist, combined with G-CSF, improves stem cell yields for transplantation. This chemokine axis-mobilization strategy enhances engraftment and may offer benefits in tissue repair.

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Generation of Human Induced Pluripotent Stem Cells from Peripheral Blood Using the STEMCCA Lentiviral Vector

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Area of Science:

Hematology
Stem Cell Biology
Immunology

Background:

Bone marrow (BM) hematopoietic stem cells (HSC) are crucial for treating hematologic diseases.
Peripheral blood HSC (PBSC) mobilization offers advantages over BM HSC, with G-CSF being the current standard mobilizer.
The SDF-1/CXCL12 and CXCR4 axis is a key regulator of HSC trafficking.

Purpose of the Study:

To evaluate the efficacy of AMD3100, a CXCR4 antagonist, in mobilizing HSC for transplantation.
To compare the effectiveness of G-CSF combined with AMD3100 versus G-CSF alone for PBSC mobilization.
To assess the engraftment potential and therapeutic utility of AMD3100-mobilized PBSC.

Main Methods:

Clinical trials involving G-CSF and AMD3100 for PBSC mobilization.
Assessment of stem cell yields and patient eligibility for transplantation.
Evaluation of autologous and allogeneic transplantation outcomes with AMD3100-mobilized grafts.
Analysis of HSC homing properties.

Main Results:

Combination therapy with G-CSF and AMD3100 resulted in higher rates of achieving sufficient PBSC for transplantation compared to G-CSF alone.
AMD3100 induced rapid HSC mobilization with significant short- and long-term repopulation capacity.
Transplantation of AMD3100-mobilized grafts showed prompt and stable engraftment.
AMD3100-mobilized PBSC exhibited enhanced homing properties.

Conclusions:

Chemokine axis-mobilization using AMD3100 offers a superior strategy for PBSC harvesting, particularly in patients who are difficult to mobilize.
This approach increases cell yields and ensures prompt engraftment, potentially expanding therapeutic applications.
AMD3100-mobilized PBSC may hold promise for tissue repair and regeneration beyond transplantation.