Hematopoietic Stem Cells

Hematopoietic stem cell (HSC)

Multipotent stem cell capable of self-renewal and differentiation into all blood cell lineages that maintains long-term hematopoiesis

Hematopoietic progenitor cell (HPC)

More differentiated precursor cell derived from stem cells that contributes to early engraftment but has limited self-renewal

Hematopoietic stem cell transplant (HSCT)

Replacement of a recipient’s bone marrow with hematopoietic stem/progenitor cells to restore hematopoiesis and immune function

Purpose of HSCT

Restore normal blood cell production and immune function after bone marrow failure, malignancy treatment, or genetic disease

Autologous transplant

Stem cell transplant using the patient’s own previously collected stem cells

Syngeneic transplant

Stem cell transplant using cells from a genetically identical donor, usually an identical twin

Xenogeneic/Allogeneic transplant

Stem cell transplant using cells from a donor of a different species

Heterologous transplant

Transplant between genetically different individuals of the same species

High-dose chemotherapy purpose in HSCT

Destroys malignant cells but also destroys bone marrow, requiring stem cell rescue

Hematopoiesis

Process of blood cell production and differentiation occurring primarily in bone marrow

Average lifespan of RBCs

Approximately 120 days

Average lifespan of platelets

Approximately 7 days

Average lifespan of granulocytes

Less than 1 day

Daily blood cell turnover

Approximately 10¹² blood cells are produced and destroyed daily

Self-renewal (stem cells)

Ability of stem cells to replicate indefinitely while maintaining an undifferentiated state

Multipotency

Ability of hematopoietic stem cells to differentiate into multiple blood cell lineages

Long-term engraftment

Ability of transplanted stem cells to permanently repopulate bone marrow and maintain hematopoiesis

Common indications for HSCT

Hematologic malignancies, bone marrow failure, genetic disorders, immunodeficiency diseases, and some autoimmune diseases

Examples of hematologic malignancies treated with HSCT

Acute leukemia, lymphoma, and multiple myeloma

Examples of bone marrow failure disorders treated with HSCT

Aplastic anemia

Examples of genetic disorders treated with HSCT

Sickle cell disease and beta-thalassemia

Examples of immunodeficiency disorders treated with HSCT

Severe combined immunodeficiency (SCID) and Wiskott-Aldrich syndrome

Stem cell mobilization

Process of stimulating release of hematopoietic stem cells from bone marrow into peripheral blood

G-CSF (granulocyte colony-stimulating factor)

Cytokine used to stimulate bone marrow to release stem cells into circulation for collection

Mechanism of G-CSF mobilization

Stimulates stromal cells to release enzymes that detach HSCs from bone marrow stroma

Plerixafor (Mozobil)

CXCR4 antagonist that disrupts stem cell attachment to bone marrow and mobilizes them into circulation

Peripheral blood stem cell collection

Collection of mobilized stem cells from blood using apheresis

Apheresis

Procedure that separates and collects specific blood components while returning the rest to the donor

Typical peripheral stem cell collection volume

Approximately 300–600 mL product collected after processing several blood volumes

Optimal circulating CD34 count for collection

Approximately ≥30 CD34+ cells per µL indicates good collection potential

CD34 antigen

Cell surface marker used to identify hematopoietic stem and progenitor cells

Three major sources of stem cells

Bone marrow, peripheral blood, and umbilical cord blood

Bone marrow stem cell source

Stem cells collected directly from bone marrow, usually the iliac crest

Advantages of bone marrow stem cells

High stem cell concentration and lower risk of graft-versus-host disease

Disadvantages of bone marrow collection

Invasive procedure requiring anesthesia and operating room collection

Peripheral blood stem cell advantages

Higher CD34 cell counts and faster engraftment

Peripheral blood stem cell disadvantages

Higher risk of graft-versus-host disease

Umbilical cord blood stem cells

Stem cells collected from umbilical cord blood after birth

Advantages of cord blood

Less stringent HLA matching requirements

Disadvantages of cord blood

Lower cell dose and slower engraftment

Graft-versus-host disease (GVHD)

Condition where donor immune cells attack recipient tissues

Common GVHD target organs

Skin, liver, and gastrointestinal tract

Graft-versus-tumor effect

Beneficial immune response where donor cells attack residual cancer cells

ABO compatibility in HSCT

Blood group compatibility between donor and recipient that may influence transfusion support

Major ABO incompatibility

Recipient antibodies attack donor red blood cells or erythroid progenitors

Minor ABO incompatibility

Donor lymphocytes produce antibodies against recipient red blood cells

Bidirectional ABO incompatibility

Both donor and recipient possess antibodies against each other’s red blood cells

Passenger lymphocyte syndrome

Donor lymphocytes produce antibodies that destroy recipient RBCs after transplant

Timeframe of passenger lymphocyte syndrome

Typically occurs 5–16 days after stem cell infusion

Red cell reduction

Processing step to remove RBCs from graft in major ABO incompatibility

Plasma reduction

Processing step to remove plasma and antibodies in minor ABO incompatibility

Cryopreservation

Process of freezing stem cell products for long-term storage

Cryoprotectant used in stem cell storage

Dimethyl sulfoxide (DMSO)

Purpose of DMSO

Protects cells from osmotic damage and ice crystal formation during freezing

Storage temperature for stem cell products

Liquid nitrogen storage around −196°C

Quality control purpose in stem cell processing

Ensure safety, purity, potency, and stability of cellular products

CD34 enumeration test

Flow cytometry test used to quantify stem cells in the graft

Clonogenic assay (CFU assay)

Test measuring the ability of stem cells to grow and form colonies in culture

Sterility testing

Culture testing used to detect microbial contamination in graft products

Cell viability testing

Assessment of living versus dead cells before transplantation

Trypan blue viability test

Vital dye test where viable cells exclude dye and dead cells stain blue

Principle of trypan blue test

Nonviable cells with damaged membranes absorb dye while viable cells remain unstained