CD34+ progenitor cells: From blood production to immunity

CD34⁺ hematopoietic progenitor cells (HPCs) are the proliferative intermediates that drive day-to-day renewal of the blood and immune cells. Arising from hematopoietic stem cells, HPCs have limited self-renewal but a robust capacity to expand and differentiate into lineage-restricted myeloid and lymphoid progeny. Read on to learn about the role of CD34⁺ HPCs and other CD34+ populations and how to expand them.

CD34 is a transmembrane sialomucin protein that regulates cell adhesion and migration.^1,2 CD34 is commonly used as a marker to identify hematopoietic stem and progenitor cells (HSPCs), which are the reservoir of mature blood cell types throughout the lifetime.¹

CD34 is not exclusively hematopoietic; it is also expressed on several progenitor populations throughout the body.¹ Although CD34+ cells are generally not pluripotent, they are multipotent to generate multiple cell types within a specific lineage.³ For example, CD34+ hematopoietic stem cells (HSCs) can produce all blood and immune cell types but cannot become neurons or muscle cells.⁴

The uses and biological functions of CD34 include:

• Transplantation: CD34 is used as a marker to identify and enrich human hematopoietic stem cells for bone marrow transplantation.²
• Adhesion molecule: CD34 binds to vascular selectins, regulating stem cell homing to bone marrow microvasculature.^2,5
• Progenitor marker: In addition to HSPCs, CD34 is also expressed in endothelial progenitors and other tissue-specific stem cell populations.¹

Explore our marker defined blood cell populations

Hematopoietic stem and progenitor cells (HSPCs) are a rare population of cells in the bone marrow. They continuously renew themselves and generate all mature blood cells (red cells, white cells, platelets) to maintain the blood system throughout life.⁶

Blood cells have a relatively short lifespan. For example, red blood cells last about 120 days, and certain white blood cells survive only hours.⁷ HSPCs are responsible for maintaining lifelong production of mature blood cells through tightly regulated self-renewal and differentiation programs.⁸ 

The terms CD34+ HSCs and progenitor cells are often used interchangeably to describe the cells that produce mature blood cells. Collectively, these are referred to as hematopoietic stem and progenitor cells (HSPCs).⁶ However, there are differences between these subsets regarding their origin (ontogeny), self-renewal potential, differentiation potency, and proliferative state.⁹  

Although CD34+ HSCs typically remain quiescent at the apex of the hematopoietic hierarchy to preserve lifelong self-renewal, CD34+ HPCs are actively cycling populations committed to differentiation.^10–12 Furthermore, the broader category of CD34+ progenitor cells may also include non-hematopoietic lineages, such as endothelial progenitor cells (EPCs), which are vital for vascular repair and vasculogenesis.¹³

Explore our AppNote on the expansion of primitive hematopoietic progenitor cells.

This hierarchical organization of hematopoietic stem and progenitor cells ensures efficient blood production, depending on the requirements. HSCs maintain the stem cell reservoir required for regenerating the entire hematopoietic system, whereas HPCs generate mature lineage-specific blood cells.¹⁸ 

CD34+ hematopoietic stem and progenitor cells can differentiate into all types of blood and immune cells, forming the foundation of both the hematopoietic system and immune system. The differentiation of CD34+ HSPCs begins with cells committing to either a myeloid or a lymphoid lineage.¹⁸

Myeloid differentiation begins with HSC/HPC generating common myeloid progenitors (CMPs), which differentiate into granulocyte-macrophage progenitors (GMPs). Mature cells derived from GMPs include monocytes, macrophages, neutrophils, eosinophils, basophils, dendritic cells, and red blood cells. G-CSF, M-CSF, and GM-CSF are among the cytokines that promote myeloid differentiation.^19,20

During lymphoid differentiation, common lymphoid progenitors (CLPs) arise from HSC/HPC. CLPs generate T lymphocytes and B lymphocytes, which form the backbone of adaptive immunity, as well as natural killer (NK) cells. IL-7 and IL-2 promote lymphoid development.^19,21

The lymphoid and myeloid differentiation pathways are dynamic. During infection, cytokine signals can skew production toward immune cells. After blood loss, erythropoietin promotes the development of red blood cells.¹⁹ 

In research, HPCs serve as models to study how blood cells develop and differentiate into various cell types. Researchers are using CD34+ HSPCs to study hematopoiesis, stem cell aging, and stem cell dysfunction.²² Recently, researchers used CD34+ progenitors to produce therapeutic CAR-NK cells to target solid tumors and leukemias.²³ Additional applications of CD34+ cells in research include screening drugs affecting blood cell development and developing organ-on-a-chip systems incorporating immune components.²⁴

Researchers use CD34+ HSPCs as target cells for gene therapy because modifications persist throughout the patient’s lifetime.^25,26 Moreover, the multipotency of CD34+ HSCs and their ability to engraft make these cells valuable for transplantation and development of gene and cell therapies.²⁷ This makes HSPC and HSC gene therapy a one-time, potentially curative approach for inherited blood disorders, such as sickle cell disease.

Explore key media requirements to transition to cell therapy applications

Maintaining the multipotency of CD34+ cells during cell culture is a critical challenge for translating therapies from the lab to the clinic, as cytokines and growth factors in the serum can promote premature CD34+ cell differentiation.²⁸ Expanding CD34+ hematopoietic progenitor cells ex vivo without differentiation requires the use of serum-free, chemically defined culture systems. 

Serum-free, xeno-free formulations provide:

• Consistent, defined chemical composition for reproducible expansion. 
• Reduced differentiation pressure, maintaining CD34 expression and multipotency.
• Regulatory-friendly manufacturing compatible with GMP requirements.
• Enhanced ability to study specific cytokine effects.

Get insights into our cell culture media formulations

We offer high-quality optimized cell culture media that support the complete workflow of CD34+ cell expansion, from research to clinical-grade cell therapy.

• Hematopoietic Progenitor Cell Expansion Medium XF is a serum-free, xeno-free medium for expansion of primitive CD34+ HPCs. The medium, when combined with Cytokine Mix E, can support a 50-200-fold expansion of CD34+ progenitor cells.
• PromoExQ HPC Expansion Medium XF offers excipient GMP-grade quality with complete documentation to support scalable manufacturing and regulatory submissions. 

These tools can help you expand primitive hematopoietic progenitor cells reliably, whether you’re optimizing basic protocols or advancing clinical applications.

Contact our scientific support team to learn more about our solutions for CD34+ cell research and manufacturing and to discuss your research needs. Whether you’re investigating blood cell development, optimizing expansion protocols, or developing clinical cell therapies, we’re here to help you advance your research with the high-quality cells and media you need to succeed.

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