Peripheral Blood Stem Cell

Introduction

Hematopoietic stem cells serve as the precursors for the hematopoietic and lymphoid systems. Their distinguishing feature lies in their ability to generate cells of myelomonocytic, erythroid, megakaryocytic, and lymphoid lineages through proliferation and differentiation. Additionally, they can sustain hematopoiesis over the long term through self-renewal. The scarcity of these stem cells has posed challenges in identification, partially addressed by the advancement of functional assays and immuno-phenotyping techniques. This article will explain peripheral blood stem cells and their uses.

What Is Peripheral Blood Stem Cell?

Extensive documentation confirms that bone marrow originates from cells found in peripheral blood. Hematopoietic stem cells (HSCs) are notably dormant, versatile cells capable of self-renewal and differentiation. Following fetal development, HSCs reside in the adult bone marrow and play a vital role in replenishing various hematopoietic lineages, including lymphoid, megakaryocytic, erythroid, and myeloid, throughout adulthood. Noteworthy observations have suggested that mesenchymal stem cells (MSCs) introduced systemically may migrate back to bone marrow, hinting at their potential residency there. Recent findings indicate the possibility of mature cells, such as endothelial cells (ECs), entering the bloodstream.

A separate study investigated the fate of muscle progenitor cells injected into the circulation of lethally irradiated recipient mice alongside identifiable bone marrow cells. All recipients demonstrated significant engraftment of muscle-derived cells, representing all major adult blood lineages. Taken together, these findings strongly suggest a continuous exchange of cells between bone marrow and peripheral blood. Conversely, studies involving bone marrow transplantation have suggested the potential reversal of this process, with cells from peripheral blood repopulating the bone marrow.

Typically, most hematopoietic stem cells remain stationary within the bone marrow under normal circumstances, and they prefer to return to the marrow when administered intravenously. Although the exact mechanisms of homing are not fully understood, they involve reciprocal recognition and binding between cell surface adhesion molecules expressed by stem cells and specific ligands or counter-receptors expressed in a tissue-specific manner by vascular endothelial cells, stromal cells, and the extracellular matrix. In normal individuals, only a small fraction of hematopoietic stem cells circulate in the peripheral blood. However, larger quantities of peripheral blood stem cells may be observed under certain pathological or iatrogenic conditions discussed below. Whether this increase results from disturbances in the bone marrow microenvironment or alterations in the profile of stem cell adhesion molecules remains unclear.

What Is Peripheral Blood Stem Cell Transplantation (PBSCT)?

There are three potential advantages of peripheral blood stem cell transplantation (PBSCT) over autologous bone marrow transplantation. Firstly, PBSCT can be harvested without requiring healthy pelvic bone marrow or general anesthesia, making it a viable therapeutic option for patients with marrow damage from prior disease or radiotherapy.

Secondly, rapid hematopoietic reconstitution is observed in patients transplanted with PBSCT collected after mobilization. The infusion of adequate numbers of colony-forming unit-granulocyte macrophages (CFU-GM) correlates well with granulocyte recovery rates, achieving neutrophil and platelet counts comparable to steady-state autologous bone marrow transplantation (AutoBMT), but with shorter engraftment times, reducing patient morbidity and resource utilization.

The speed of hematopoietic reconstitution may be related to a higher proportion of myeloid-committed stem cells in mobilized PBSCT harvests. However, concerns have been raised regarding the presence of pluripotential hematopoietic stem cells necessary for long-term engraftment in PBSCT.

Although some studies in animals and humans have demonstrated long-term recovery of hematopoiesis after PBSCT, it is unclear if this signifies sustained engraftment due to the survival of endogenous hematopoietic stem cells post-chemoradiotherapy and the possibility of initial transient PBSCT-generated hematopoiesis being replaced by endogenous recovery.

Lastly, PBSCT may offer a lower risk of tumor contamination than bone marrow harvest, particularly in certain malignancies. However, further research is needed to ascertain the extent of this advantage and its impact on relapse rates post-transplantation.

What Are the Future Uses of Peripheral Blood Stem Cell Transplantation?

The following are the uses of peripheral blood stem cell transplantation:

• Allogenic PBSCT - Initially, allogeneic peripheral blood stem cell transplantation (PBSCT) was primarily considered for cases of graft failure necessitating a second infusion of stem cells and for donors who were unsuitable candidates for general anesthesia. However, there has been a recent increase in allogeneic PBSCT procedures, with corresponding studies emerging. Typically, granulocyte colony-stimulating factor (G-CSF) at a dosage of 5-10 μg/kg/day for four to five days is the most commonly utilized method for mobilization. Engraftment is generally achieved rapidly with a minimum threshold dose of 3 × 106 CD34+ cells/kg body weight. This target can often be met with a single apheresis session, which enhances donor acceptability. Nevertheless, in some cases, donors may fail to mobilize, necessitating a bone marrow harvest instead.

• Cord-Blood Transplant (Cbt)- Abundant levels of stem and progenitor cells with robust renewable and proliferative capabilities are found in cord blood. This inherent physiological condition of cord blood presents a distinct opportunity to collect peripheral blood stem cells (PBSCs), which would otherwise go unused in quantities suitable for transplantation. The inaugural cord blood transplantation (CBT) was documented in 1989 by Gluckman et al., involving a child with Fanconi's anemia who received cord blood from an HLA-identical sibling.

• Ex-vivo Manipulation of PBSC - The continuous pursuit of processing blood or marrow cells in laboratory settings to achieve therapeutic objectives has been ongoing. Mobilization of peripheral blood stem cells (PBSC) has emerged as a method to procure stem cells in abundant quantities with comparative simplicity, counterbalancing the cell loss incurred during these manipulations outside the body. Areas of oncological focus include tumor purification, immunomodulation, hematopoietic cell expansion, and gene therapy.

Conclusion

Over the past decade, around 500 peripheral blood stem cell transplants have been documented, predominantly as autologous transplants in patients diagnosed with acute or chronic leukemia, lymphoma, myeloma, or solid tumors. This procedure offers notable advantages over bone marrow transplantation for patients with marrow disorders, significantly accelerating hematopoietic reconstitution while reducing procedure-related morbidity and mortality.

Despite initial concerns about the long-term restoration of hematopoiesis, clinical evidence suggests this is generally not an issue. However, the extent to which it relies on infused pluripotential stem cells versus endogenous stem cells surviving the conditioning regimen remains uncertain. Further advancements in characterizing hematopoietic stem cells from various sources, developing less toxic and more efficient mobilization methods, and refining the timing of leukapheresis are crucial to enhancing peripheral blood stem cell transplantation and expanding its application to allogeneic settings or gene therapy. Early indications of differing levels of minimal residual disease between bone marrow and peripheral blood stem cell harvests may position the latter as the preferred procedure for certain neoplastic diseases.