Critical Limb Ischemia.  3 Things to Know.

The Race Against Amputation: Understanding Critical LimbThreatening Ischemia

Every year, approximately 150,000-200,000 Americans under go major lower extremity amputations. The primary driver: critical limb threatening ischemia (CLTI)—severe blockages in leg arteries that deprive tissue of oxygen to the point of death. Without intervention, roughly 40% ofCLTI patients will lose their leg within six months, and 20% will die within one year.

These statistics reveal a stark reality: CLTI represents amedical emergency, not a chronic condition to manage. Yet many patients receivetheir diagnosis only after symptoms have progressed to advancedstages—non-healing wounds, rest pain, or tissue death. By then, treatment options narrow dramatically, and the race against amputation has already begun.

What Is Critical Limb Threatening Ischemia?

CLTI is the most severe form of peripheral artery disease(PAD). It occurs when atherosclerotic plaque severely narrows or completely blocks the arteries supplying blood to the legs and feet. Unlike claudication(leg pain with walking that resolves with rest), CLTI causes:

Ischemic rest pain: Severe, unrelenting pain in the foot or toes, especially when lying down at night. This occurs because even at rest, the tissues aren't receiving adequate oxygen.

Non-healing wounds or ulcers: Minor injuries that would normally heal in days or weeks instead persist for months. Without adequate blood flow, the body cannot deliver the oxygen, nutrients, and immune cells necessary for wound healing.

Gangrene: Tissue death (necrosis) in toes, feet, orlarger portions of the leg. The tissue turns black as cells die from oxygen starvation.

The diagnostic criteria are objective: ankle-brachial index(ABI) below 0.4, toe pressure below 30 mmHg, or transcutaneous oxygen pressure below 30 mmHg. These measurements confirm that blood flow has dropped to critically insufficient levels.

Who Develops CLTI?

CLTI affects approximately 2-3 million people in the UnitedStates, with several high-risk populations:

Diabetic patients: Diabetes dramatically accelerates atherosclerosis and damages both large and small blood vessels. Diabetics withPAD are 5-10 times more likely to require amputation than non-diabetics with similar disease severity.

Chronic kidney disease patients: Kidney dysfunction promotes vascular calcification, creating exceptionally hard, difficult-to-treat arterial blockages.

Smokers: Tobacco use is the single strongest modifiable risk factor for PAD progression to CLTI.

Elderly patients: Age-related vascular changes, combined with accumulated atherosclerotic burden, increase CLTI risk.

The common thread: these populations have impaired ability to develop collateral circulation—the natural bypass networks the body creates blockages. When collateral formation fails, even moderate arterial disease can progress rapidly to CLTI.

Current Treatment Options: Revascularization

The gold standard treatment for CLTI is revascularization—restoring blood flow through either:

Endovascular procedures: Angioplasty (balloon inflation) and stenting to open blocked arteries from inside the vessel. This minimally invasive approach works best for focal, accessible blockages.

Surgical bypass: Creating a detour around blockages using vein grafts or synthetic conduits. This open surgery is more invasive but can treat longer, more complex blockages.

When revascularization succeeds, outcomes improve dramatically: wounds heal, pain resolves, and limb salvage rates increase.Large trials have confirmed that successful revascularization reduces amputation risk by 60-80%.

But here's the critical problem: approximately 30-40%of CLTI patients are not candidates for traditional revascularization. Their disease is too diffuse, their vessels too calcified, their anatomy too unfavorable, or their medical comorbidities too severe to tolerate surgery.

These 'no-option' CLTI patients face a devastating prognosis: without revascularization, one-year amputation rates approach40-50%.

The Treatment Gap: When Revascularization Isn't Possible

For patients who cannot undergo traditional revascularization, options are limited and largely palliative:

Pain management: Opioids for ischemic rest pain, though these address symptoms without fixing the underlying problem.

Wound care: Debridement, offloading, infection control—all necessary but insufficient when blood flow remains critically low.

Amputation: Often presented as the only remaining option when tissue loss progresses despite conservative measures.

This is where regenerative medicine offers something fundamentally different: the potential to grow new blood vessels, creating natural bypass networks that traditional surgery cannot.

Therapeutic Angiogenesis for CLTI: A Biological Approach

The rationale for angiogenic therapy in CLTI is straight forward: if the problem is inadequate blood flow due to blocked arteries, and traditional methods to restore flow have failed or aren'tpossible, can we stimulate the body to grow entirely new blood vessels?

The body attempts this naturally through collateral vessel formation—small arterial branches that enlarge and create detour routes around blockages. But in CLTI patients, this natural process is either too slow or insufficiently robust to prevent tissue death.

Angiogenic cell therapy aims to amplify this natural mechanism by delivering cells that:

Release high concentrations of growth factors (VEGF, FGF,HGF) that signal blood vessels to sprout and grow

Recruit the patient's own endothelial progenitor cells from bone marrow to participate in vessel formation

Create a more favorable microenvironment for angiogenesis byr educing inflammation and supporting tissue repair

The goal isn't to replace a single blocked artery with a single bypass graft. It's to create a network of many small new vessels—ad istributed circulation system that collectively restores adequate blood flow to ischemic tissue.

ACP-01 for Critical Limb Threatening Ischemia

Hemostemix's ACP-01 (Angiogenic Cell Precursors) has been specifically studied in CLTI patients—particularly those deemed 'no-option' candidates for traditional revascularization.

The treatment approach:

Patient's own blood is collected through a standard blood draw (autologous cells—no donor required, no rejection risk).

Cells are processed and expanded in the laboratory to isolate those with strong angiogenic potential—cells that naturally produce high levels of vascular growth factors.

Cells are delivered via intramuscular injection directly into the ischemic muscles of the leg and foot. This can be done as an outpatient procedure under local anesthesia.

Once delivered, the cells act as biological factories, continuously releasing angiogenic signals that stimulate new blood vessel formation over the following weeks and months.

Clinical Evidence in CLTI

Hemostemix has conducted clinical trials specifically in no-option CLTI patients—those who had failed or were unsuitable for conventional revascularization. Key findings include:

Limb salvage rates: Studies have shown amputation-free survival rates exceeding historical controls for no-option CLTI patients. While these patients would typically face 40-50% amputation rates within one year, treated patients showed significantly lower amputation rates.

Wound healing: Patients with ischemic ulcers showed improvements in wound healing, with some achieving complete closure of wounds that had been present for months or years.

Pain reduction: Improvements in ischemic rest pain scores, with many patients able to reduce or eliminate opioid pain medications.

Perfusion improvements: Objective measurements(transcutaneous oxygen pressure, ankle-brachial index) showed improvements in tissue oxygenation, documenting that new blood vessels had formed and were delivering oxygen to previously ischemic tissue.

Safety profile: ACP-01 has been administered to 498 patients across multiple conditions with no significant safety concerns.Because the cells are autologous (from the patient's own blood), there's norisk of immune rejection.

These results align with broader research on cell-based therapies for CLTI. Multiple clinical trials and meta-analyses have demonstrated that angiogenic cell therapy can reduce amputation rates and improve limb salvage in no-option patients.

Who Should Consider ACP-01 for CLTI?

ACP-01 is being studied for CLTI patients who:

Have critical limb threatening ischemia with rest pain, non-healing wounds, or tissue loss

Are not candidates for surgical or endovascular revascularization (no-option patients)

Have failed previous revascularization attempts

Face amputation as the only remaining conventional option

The ideal timing is before extensive tissue loss has occurred. While ACP-01 can stimulate new blood vessel growth, it cannot reverse dead tissue. Earlier intervention—when viable but severely ischemic tissue remains—offers the best opportunity for limb salvage.

Taking Action: What CLTI Patients Should Know

If you've been diagnosed with critical limb threatening ischemia and told that revascularization isn't possible, or if previous revascularization procedures have failed, regenerative medicine represents a biologically distinct option worth exploring.

Key steps:

Confirm your no-option status: Ask your vascular surgeon or interventional radiologist: 'Have all revascularization options truly been exhausted?' Sometimes a second opinion at a specialized center reveals options that weren't initially apparent.

Research angiogenic therapy trials: Visithemostemixclinicaltrials.com to learn about ongoing ACP-01 studies for CLTI, eligibility criteria, and participating centers.

Act promptly: CLTI progresses rapidly. Tissue death is irreversible. The window for limb salvage narrows with each passing week.Don't wait until amputation is imminent.

Optimize other factors: While pursuing angiogenic therapy, continue aggressive wound care, infection control, pressure offloading, smoking cessation, and diabetes management. These interventions support but don't replace the need to restore blood flow.

Learn More About ACP-01 for CLTI:

Visit: hemostemixclinicaltrials.com

Important Note: ACP-01 is currently beinge valuated in clinical trials for CLTI and is not yet FDA-approved for general use. Information presented here is for educational purposes and does not constitute medical advice. Consult your vascular surgeon about whether regenerativemedicine options may be appropriate for your specific condition.