Stem Cell Mobilization - Importance and Types

Introduction:

Stem cells are known as the raw material of the human body. These are the cells from which all other cells with special functions arise. Under proper conditions in the body or laboratory, stem cells divide to form more cells, so-called daughter cells. These daughter cells turn into new stem cells or specialized cells (differentiation) with more specific functions, such as blood cells, brain cells, cardiomyocytes, and osteocytes. Other cell types in the body do not have the natural ability to create new cell types. Stem cells are available from various sources, including amniotic fluid cells, umbilical cord, placental tissue, adipose tissue, and bone marrow. A premature cell that can evolve into any type of blood cell, including white blood cells, red blood cells, and platelets, is called a hematopoietic stem cell. They are present in peripheral blood and bone marrow. They are also termed blood stem cells.

What Is the Importance of Stem Cells?

The importance of stems cells is explained below in detail:

• To Improve the Understanding of How the Disease Develop - By observing how stem cells mature into cells in bone, heart muscle, nerves, and other organs and tissues, researchers may be able to understand and research how diseases and conditions develop.

• Regenerative Medicine - Stem cells generate healthy cells to replace diseased cells. Stem cells can be further transformed into specific cell types that humans can use to repair and regenerate tissues that have been damaged or affected by a disease. Stem cells have the potential to grow into new tissue for use in transplantation and regenerative medicine. Medical researchers continue to expand their knowledge of stem cells and their applications in transplantation and regenerative medicine.

• To Test the Safety and Efficacy of New Drugs - Before an investigational drug is used in humans, researchers can use several types of stem cells to test the drug's safety and quality. This type of test will initially directly impact drug development for cardiotoxicity testing.

What Is Stem Cell Mobilization?

A process that involves certain pharmacological agents to move stem cells from the bone marrow into the blood. Stem cells can be collected and stored. These can later be utilized as bone marrow replacements in stem cell transplantation. Stem cell mobilization is the process of stimulating stem cells from the bone marrow cavity (such as the hipbone or breastbone) into the bloodstream so that they can be collected for later reinfusion. Cells are then stored, frozen, and preserved until transplantation.

Hematopoietic cell transplantation is a life-saving therapy for many hematologic malignancies and some solid tumors. The use of granulocyte colony-stimulating factor (G-CSF) mobilization into the peripheral blood stem cells (PBSCs) has largely replaced bone marrow (BM) as the source of stem cells for both autologous and allogeneic cell transplantation.

What Are the Main Stem Cell Mobilization Agents?

The main stem cell mobilizers are listed below:

• Granulocyte Colony-Stimulating Factor (G-CSF) - G-CSF remains clinically the most commonly used agent for hematopoietic stem cell mobilization. The most commonly given dose of G-CSF is 10 μg/lb/day, given through subcutaneous injection.

• Plerixafor - It is a bicyclam molecule that reversibly inhibits the binding of SDF-1 to CXCR4, thereby promoting hematopoietic stem cell (HSC) recruitment. Plerixafol is approved in combination with G-CSF for stem cell mobilization in myeloma (cancer of plasma cells) and lymphoma (cancer of lymphatic cells) patients. Plerixafor's high cost limits its universal use. Some centers have developed risk-adapted algorithms for optimal drug use and administer plerixafor only to patients at high risk of mobilization failure.

• Stem Cell Factor (SCF) - Stem cell factor, also known as C-Kit ligand (KITL), is a growth factor of hematopoietic origin produced by endothelial and perivascular stromal cells in the bone marrow niche. Recombinant human SCF combined with G-CSF has been shown to increase stem cell yield.

• Chemotherapy - Chemotherapy is commonly used for stem cell mobilization in autologous stem cell transplantation. Specially selected agents are generally disease-specific and are used to reduce tumor burden and promote mobilization. Cyclophosphamide (CY) is one of the most commonly given chemotherapeutic agents for cancer therapy.

What Are the Side Effects of Stem Cell Mobilizers?

Side effects of stem cell mobilizers include the following:

• Nausea and vomiting.

• Diarrhea.

• Dizziness.

• Headache.

• Difficulty breathing.

• Increased heart rate.

• Easy bruising or bleeding.

• Injection site reactions.

• Abdominal pain.

• Tiredness.

• Joint pain.

• Anaphylaxis (life-threatening allergic reactions).

How Do Stem Cell Mobilizers Work?

Stem cell mobilizers work in the ways listed below:

• G-CSF - It is the most clinically relevant mobilizing agent. It increases the number of stem cells while simultaneously inducing their proliferation and maturation to the granulocytic lineage and causing marked changes in the hematopoietic stroma within the bone marrow. These changes result in the release or recruitment of hematopoietic stem cells.

• Plerixafor - It is a selective chemokine receptor (CXCR4) antagonist. It inhibits the binding of the CXCR4 chemokine receptor to stromal cell-derived factor 1-α, resulting in the release of HSCs from the bone marrow and their recruitment into the peripheral circulation, where they are then collected and transfused into the body.

• Stem Cell Factor - It binds to the c-KIT receptor expressed on HSCs. Activation of these receptors increases the number, differentiation, and activation of circulating peripheral blood progenitor cells such as CD34, granulocyte-macrophage colony-forming units, and erythroid burst-forming units. These progenitor cells are collected and later transfused into the body.

In Which Conditions Are Stem Cell Mobilizers Used?

Stem cell mobilizers are given as subcutaneous injections for transplantation of autologous blood in patients with:

• Blood cancers.

• Non-Hodgkin’s lymphoma (malignant cancer of the lymph system).

• Multiple myeloma (cancer of plasma cells).

• Following chemotherapy.

Conclusion:

Mobilization of the hematopoietic stem can be achieved through various niche modifications in the bone marrow, but efficient mobilization requires simultaneous expansion of the stem cell pool. Future challenges regarding hematopoietic stem cell mobilization include analysis of genetic factors responsible for large variations in mobilization responses, identification of predictors of mobilization efficiency, and development of mobilization schemes for weak mobilizers. Moreover, improving therapeutic regimens to enhance or even prioritize the mobilization of non-hematopoietic stem cell types and their therapeutic potential in intrinsic tissue repair will be vigorously pursued in the near future for the successful treatment of cancers.