Bone marrow transplantation offers an effective solution to hematological disorders which has no other curative therapy. It has led to significant research into bone marrow cell populations, resulting in the discovery of mononuclear cells. They refer to the immune cells found either in the bone marrow or peripheral blood. However, both sources comprise different cell types. While peripheral blood contains mature immune cells in its mononuclear cell fraction, human bone marrow-derived mononuclear cells have progenitors. These progenitors have applications in regenerative medicine for diverse disorders.
Human Bone Marrow Mononuclear Cells
Mononuclear cells refer to the leukocytes with a single nucleus. The term includes lymphocytes (T and B cells), dendritic cells, macrophages, and natural killer (NK) cells. However, bone marrow mononuclear cells (BM-MNCs) contain early progenitors of these cells, therefore comprising immature lymphocytes and monocytes. In addition, BM-MNCs are a rich source of hematopoietic stem cells (HSCs), endothelial progenitors, and Human Bone Marrow Derived Mesenchymal Stem Cells (MSCs).
BM-MNCs secrete a plethora of growth factors and cytokines, which create a microenvironment for promoting tissue regeneration. An additional advantage of using these cell fractions is the absence of an isolation step. Cells after extraction from tissue require separation from other cells to acquire a pure cell population, such as HSCs, MSCs, etc. However, BM-MNCs only need the initial washing step to remove bone marrow spicules and other debris, followed by administration.
Human Bone Marrow Mononuclear Cells
Mononuclear cells refer to the leukocytes with a single nucleus. The term includes lymphocytes (T and B cells), dendritic cells, macrophages, and natural killer (NK) cells. However, bone marrow mononuclear cells (BM-MNCs) contain early progenitors of these cells, therefore comprising immature lymphocytes and monocytes. In addition, BM-MNCs are a rich source of hematopoietic stem cells (HSCs), endothelial progenitors, and Human Bone Marrow Derived Mesenchymal Stem Cells (MSCs).
BM-MNCs secrete a plethora of growth factors and cytokines, which create a microenvironment for promoting tissue regeneration. An additional advantage of using these cell fractions is the absence of an isolation step. Cells after extraction from tissue require separation from other cells to acquire a pure cell population, such as HSCs, MSCs, etc. However, BM-MNCs only need the initial washing step to remove bone marrow spicules and other debris, followed by administration.
Applications of Bone Marrow Mononuclear Cells
Neurological Disorders: Disorders of the nervous system, such as cerebral stroke, spinal cord injury, and cerebral palsy, do not have a curative treatment. They exhibit neuroprotective and neuroregenerative properties. According to several research studies, BM-MNCs can alleviate inflammation and induce neurogenesis in animal models of stroke. They can reduce lymphocyte migration to tissue, diminishing lesion size and neural damage. A clinical trial showed improvement in white matter integrity after BM-MNCs administration. They increase the uptake of VEGF by endothelial cells and reduce endothelial autophagy in the cerebral ischemic stroke model.
Cardiovascular Disorders: These disorders are the predominant cause of mortality. BM-MNCs are beneficial in these disorders to regenerate cardiomyocytes and restore their functions. A research study demonstrated modulation of calcium concentration in cardiomyocytes and retention of their contractile ability when cultured in BM-MNC-conditioned medium. The supernatant of BM-MNCs also showed similar results in animal models by improving muscle contractility and microvessel quantity, leading to improved cardiac function. The REPAIR-AMI clinical trial has proved the therapeutic potential of BM-MNCs, recommending their use in mainstream treatments.
Angiogenesis: BM-MNCs increase the levels of angiogenesis growth factors such as bFGF, VEGF, etc. Studies have demonstrated that they secrete IL-10, which has protective effects on vessels. They contribute to neovascularization and regulate remodeling by controlling T cell migration and collagen accumulation. The angiogeneic effects of BM-MNCs are beneficial in ischemic injuries like critical limb ischemia.
Bone Regeneration: Osteoarthritis is primarily driven by inflammation. Injury recruits immune cells to prevent infection, and macrophages shift from M1 to M2, initiating repair. These mechanisms deregulate in osteoarthritis, causing significant tissue damage. The macrophage progenitors in BM-MNCs reduce inflammation and also transdifferentiate into fibrocytes that induce tissue repair. They also release growth factors such as IGF1, IL10, and PGE2 to stimulate repair. A clinical study reported improvements in the joints of 97% patients after BM-MNC treatment. Bone tissue engineering is another avenue for BM-MNCs. Researchers are studying the impact of seeding BM-MNCs on scaffolds and initial findings are showing better potential of BM-MNCs than MSCs.
Diabetes: Scientific research on type 1 and type 2 diabetes and the associated comorbidities has gained considerable pace. Regenerative therapies are slowly taking center stage for diabetes treatment. Stem Cell Treatment have shown notable improvements. This has also encouraged the utilization of BM-MNC for diabetes. Clinical trials have shown an increase in insulin levels and a decrease in comorbidities after BM-MNC treatment. This significantly reduced the need for medications. The results were attributed to paracrine signaling, immunomodulation, and cell regeneration.
Liver Damage: Liver disorders cause injury to the tissue that triggers a signaling cascade leading to fibrosis. The cells lost during damage cannot be recovered. However, the stem cell population of BM-MNCs has the capacity for liver regeneration. In animal models of liver disorders, BM-MNC treatment has improved the liver enzyme concentration along with increasing survival. The anti-inflammatory response and paracrine healing by BM-MNCs are evident by the presence of liver regeneration markers in the treated group.
Cardiovascular Disorders: These disorders are the predominant cause of mortality. BM-MNCs are beneficial in these disorders to regenerate cardiomyocytes and restore their functions. A research study demonstrated modulation of calcium concentration in cardiomyocytes and retention of their contractile ability when cultured in BM-MNC-conditioned medium. The supernatant of BM-MNCs also showed similar results in animal models by improving muscle contractility and microvessel quantity, leading to improved cardiac function. The REPAIR-AMI clinical trial has proved the therapeutic potential of BM-MNCs, recommending their use in mainstream treatments.
Angiogenesis: BM-MNCs increase the levels of angiogenesis growth factors such as bFGF, VEGF, etc. Studies have demonstrated that they secrete IL-10, which has protective effects on vessels. They contribute to neovascularization and regulate remodeling by controlling T cell migration and collagen accumulation. The angiogeneic effects of BM-MNCs are beneficial in ischemic injuries like critical limb ischemia.
Bone Regeneration: Osteoarthritis is primarily driven by inflammation. Injury recruits immune cells to prevent infection, and macrophages shift from M1 to M2, initiating repair. These mechanisms deregulate in osteoarthritis, causing significant tissue damage. The macrophage progenitors in BM-MNCs reduce inflammation and also transdifferentiate into fibrocytes that induce tissue repair. They also release growth factors such as IGF1, IL10, and PGE2 to stimulate repair. A clinical study reported improvements in the joints of 97% patients after BM-MNC treatment. Bone tissue engineering is another avenue for BM-MNCs. Researchers are studying the impact of seeding BM-MNCs on scaffolds and initial findings are showing better potential of BM-MNCs than MSCs.
Diabetes: Scientific research on type 1 and type 2 diabetes and the associated comorbidities has gained considerable pace. Regenerative therapies are slowly taking center stage for diabetes treatment. Stem Cell Treatment have shown notable improvements. This has also encouraged the utilization of BM-MNC for diabetes. Clinical trials have shown an increase in insulin levels and a decrease in comorbidities after BM-MNC treatment. This significantly reduced the need for medications. The results were attributed to paracrine signaling, immunomodulation, and cell regeneration.
Liver Damage: Liver disorders cause injury to the tissue that triggers a signaling cascade leading to fibrosis. The cells lost during damage cannot be recovered. However, the stem cell population of BM-MNCs has the capacity for liver regeneration. In animal models of liver disorders, BM-MNC treatment has improved the liver enzyme concentration along with increasing survival. The anti-inflammatory response and paracrine healing by BM-MNCs are evident by the presence of liver regeneration markers in the treated group.
Conclusion
Bone marrow has delivered two distinct stem cell populations that have revolutionized the field of regenerative medicine. Bone marrow HSCs and MSCs are used separately in treatment after a meticulous isolation process. Considering the potential of stem cells, BM-MNCs have garnered attention as an alternative for stem cell therapy. BM-MNCs combine the population of both stem cells, along with other progenitors, to offer better therapeutic effects. They eliminate the need for an extensive isolation step and are therefore employed in autologous cell therapy. Clinical trials have demonstrated favorable outcomes with BM-MNC treatment for diverse disorders. Kosheeka promotes research on BM-MNCs and their therapeutic applications with its ethically sourced and premium quality Human Bone Marrow Derived Mononuclear Cells.
Attachments
-
Potential-of-Human-Bone-Kosheeka.jpg