Critical Limb Ischemia (CLI) is a severe form of peripheral artery disease, usually associated with dismal outcomes. It often arises from multiple factors and comorbidities. The incidence of CLI in India alone exceeds 800 million cases. Approximately 10-40% of the cases have to undergo limb amputation and/or gangrene. CLI patients typically face higher chances of cardiovascular and cerebrovascular diseases, which considerably lowers their life expectancy. The progressive nature of the disease and the co-occurrence of other medical conditions increase the mortality rate in patients.
The current treatment modalities have a modest impact on outcomes, which has prompted the search for better interventions. In this pursuit, regenerative medicine appears to be a feasible option. Stem cell therapy has become the forefront of this field, offering substantial improvement in diverse disorders. Therefore, the application of Stem Cell Therapy for Critical Limb Ischemia has also been explored.
Critical Limb Ischemia (CLI)
Critical limb ischemia (CLI) or chronic limb-threatening ischemia (CLTI) is an advanced stage of peripheral artery disease. It occurs due to reduced blood flow to the lower limbs. In comparison to acute limb ischemia, CLI occurs more gradually and develops over months and years. Low blood flow to the extremities manifests as pain at rest, ulcers, non-healing wounds, numbness or tingling sensation, tissue loss, dry skin, and gangrene, which often leads to limb amputation.
The factors behind CLI include diabetes, high cholesterol, hypertension, obesity, age, family history of CLI, smoking, etc. They weaken the blood vessels or lead to plaque buildup and vessel hardening (atherosclerosis). The resultant decline in blood perfusion to the tissue and nerves causes tissue death and pain.
Treatment Limitations
The goal of CLI treatment is to restore the blood supply. It employs medications that dilate vessels or relieve pain. Angioplasty and endovascular procedures are also noninvasive treatments for widening vessels and removing obstruction, respectively. Surgical revascularization is the last option for patients who show a poor response to the already available treatments.
- However, surgery also increases the chances of vessel dysfunction.
- Depending on the site of obstruction and the comorbidities, many patients do not qualify for surgical treatments, leaving them with no treatment option.
- Some patients respond poorly to surgery and become ineligible for additional surgical treatments, categorizing them into no-option CLI.
- The treatments have a modest impact on salvaging limbs from amputation.
These limitations have fueled the research on better treatment strategies with Stem Cell Treatment for Critical Limb Ischemia, ranking at the top of the list.
Stem Cell Therapy for Critical Limb Ischemia
Stem cells have regenerative potential that stimulates tissue repair. They act on several pathways that treat the disorder, replenish the lost tissue, and improve functional recovery. In CLI, stem cell therapy governs processes related to the cells of blood vessels—endothelial cells—to regulate the disease pathways.
- Vessel Formation: Stem cells develop into endothelial cells and also secrete growth factors (FGF2, VEGF, IL8) for endothelial cell migration and proliferation. These two processes stimulate the formation of blood vessels in order to restore blood flow.
- Reduce Inflammation: Chronic inflammation exacerbates the disorder. Stem cells alleviate inflammation by releasing sTNFR, IL8, CXCL6, CXCL5, PGE2, TSG6, etc.
- Regulate Immune Response: Stem cells also induce a shift in the immune response. They polarize macrophages towards reparative M2 type and also augment the levels of regulatory T cells to favor healing.
- Tissue Regeneration: The growth factors of stem cells also accelerate the healing of CLI wounds.
Stem Cells for Critical Limb Ischemia
Diverse types of stem cells are present in the therapeutic niche. Each has its own significance and set of therapeutic properties. Here are the types of stem cells investigated for CLI.
- Bone marrow-derived mononuclear cells (BM-MNCs): These include a repertoire of immune cells and stem cells that have exhibited therapeutic effects on CLI.
- Mesenchymal stem cells (MSCs): These cells are commonly sourced from bone marrow, umbilical cord, or adipose tissue. They have immunomodulatory, anti-inflammatory, and angiogenic properties that have shown potential for CLI treatment.
- Peripheral blood stem cells: They are collected from the blood after mobilization from bone marrow using agents like G-CSF.
Most clinical trials have employed MSCs for CLI treatment. MSCs have a lower risk of immune rejection and multiple therapeutic properties that benefit the disorder.
Clinical studies have shown that Stem Cell Therapy is safe. The improvements from the therapy often last longer, spanning years. The increased blood flow results in pain relief, wound healing, increased walking time, and enhanced survival rates. With large-scale studies, this treatment will soon become a mainstay of therapies.
No-option CLI
The term “no-option” CLI encompasses cases that could not even benefit from surgical treatment and therefore do not qualify for additional surgical treatment. Surgery is typically the last alternative for CLI patients and is performed on selected patients. No-option signifies the absence of a treatment alternative for CLI patients.
Stem cell treatment has offered hope to them. Initial studies have shown that the therapy enhances blood flow in limbs, reducing pain, promoting healing of ulcers, and substantially decreasing the rate of amputation.
Critical Limb Ischemia Treatment In India
India faces a high prevalence of CLI, resulting from the increased occurrence of underlying disorders such as diabetes and hypertension in the Indian population. The country is taking measures to resolve these unique challenges. It has considerably grown its infrastructure for advanced care and clinical expertise, offering them at affordable prices.
Many specialized hospitals are also integrating stem cell treatment, particularly in research and for no-option CLI patients. The country has strengthened its regulatory framework for ethical compliance and safety in stem cell research and therapy. Many private sector players are also contributing to the CLI treatment. A key player of this ecosystem is Advancells- a stem cell manufacturer. The company has amassed strong credibility in the market with ISO-certified laboratory operations and GMP-based protocols. Its scientific team has expertise in stem cells and robustly tests each stem cell formulation.
Conclusion
CLI has a high risk of limb amputation and mortality despite the available treatments. It has promoted several innovations, among which stem cell therapy has been the most promising. It not only restores blood flow but also drives vessel remodelling and wound healing. The no-option CLI patients have also experienced noteworthy improvements for more extended periods. However, the varying impact of the treatment has urged for swift standardization of stem cell sources, dosage, and duration of the therapy. More refined protocols can maximize the treatment outcomes. India has been drawing interest for coupling therapeutic interventions with regenerative medicine. In the coming years, stem cell therapy will yield better outcomes for CLI. Advancells, driven by compassion and patient satisfaction, is accelerating the pace of such treatments with its premium-quality stem cells. These advances are a path forward to a promising future for Stem Cells for Critical Limb Ischemia patients.
FAQ’s
Q- What is critical limb ischemia?
It is an advanced stage of peripheral artery disease marked by severely reduced blood flow to the limbs, leading to pain, ulcers, tissue loss, and an increased risk of limb amputation and death.
Q- What are the common symptoms of CLI?
Common symptoms of Stem Cells for Critical Limb Ischemia include rest pain or numbness in the feet, non-healing wounds or ulcers, shiny and dry skin, thickened toenails, and diminished pulses. The diagnosis is confirmed using objective tests like the ankle-brachial index and imaging to assess blood flow impairment.
Q- How do stem cells help in the treatment of CLI?
Stem cells support tissue repair, stimulate blood vessel formation, reduce inflammation, and regulate immune responses. It results in improved limb function, pain reduction, and higher amputation-free survival even for patients not eligible for traditional surgery.
Q- Is stem cell treatment for CLI safe?
Clinical research demonstrates the safety and long-term benefits of stem cell treatment. But before it becomes a common treatment, more study and standards are required. For wider access, India is aggressively developing its regulatory and infrastructure frameworks.
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