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INTERVENTIONAL RADIOLOGY INNOVATION AT STANFORD

AVNESH S THAKOR MD PHD

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Locoregional targeted delivery for improved therapeutic outcomes

Interventional Radiologists can access almost any part of the human body without the need for conventional open surgical techniques. As such, they are poised to change the way patients can be treated, given they can locally deliver drug, gene, cell and cell-free therapies directly to affected organs using image-guided endovascular (i.e. within blood vessels), endoluminal (i.e. within the bowel, respiratory or urinary system), percutaneous (i.e. through the skin) and even using device implantation (i.e. bioscaffolds) approaches. These Precision Delivery approaches overcome many of the issues related to conventional systemic delivery of therapies which includes: first-pass drug metabolism, off-target side effects, lung entrapment of cellular therapies and liver/spleen entrapment of nano or micro scale cell-free and gene-vector therapies

Our lab develops new pre-clinical translational models for locoregional precision delivery of therapeutics into different organ systems with the vision that these can be effectively clinically translated into patients. Given the foundation of Interventional Oncology (IO), where we treat solid tumors through the local delivery of drug, cellular and thermal/ablative therapies, our team is pioneering the new scientific field of Interventional Regenerative Medicine (IRM), where we envisage the ability to restore cellular health and function of injured tissues through the local delivery of stem cell therapies.

PRECISION DELIVERY

DIABETES

KIDNEY INJURIES

KIDNEY INJURIES

ARDS (LUNG INJURY)

ARDS
(LUNG INJURY)

INFLAMMATORY BOWEL DISEASE

INFLAMMATORY
BOWEL DISEASE

ALZHEIMER'S DISEASE

ALZHEIMER'S
DISEASE

PANCREATIC CANCER

PANCREATIC
CANCER

BIOSCAFFOLDS

PRECISION EQUIPMENT

PRECISION
EQUIPMENT

Diabetes is characterized by the inability to regulate blood glucose levels. Early in the disease process, our research focuses on regenerating the native pancreas, protecting islets and modulating the immune system through locoregional delivery of MSC therapies directly into the pancreas via its arterial blood supply. Later in the disease process, our research focuses on optimizing islet transplantation, which can provide new insulin-producing beta-cells to patients, using tissue bioengineering and MSC approaches. Islet transplantation is an example of how Interventional Radiologists play a central role in the delivery of cell therapies, with islet cells conventionally delivered into the liver of patients using minimally invasive percutaneous approaches.

Acute Kidney Injury (AKI) occurs in a significant number of hospitalized patients, especially in those receiving chemotherapy or undergoing cardiovascular procedures. While many patients recover, the kidneys are often left with residual damage which predisposes them to develop kidney dysfunction or chronic kidney disease in later life. Our research focuses on stimulating a regenerative phenotype in the injured kidney following through locoregional delivery of MSC therapies into the kidney via the renal artery.

Acute Respiratory Distress Syndrome (ARDS) is defined by the acute onset of pulmonary edema, hypoxia and need for mechanical ventilation. Following the recent pandemic, ARDS was a major complication of COVID-19 and was associated with significant long-term morbidity and mortality. Our research focuses on how MSC therapies can regenerate the damaged lung, maintain the epithelial-endothelial barrier and restore the bioenergetic health and function of injured cells. More specifically, we are testing the optimal way to deliver these therapies directly into the lungs, specifically examining aerosolization of our therapeutic candidates.

Inflammatory Bowel Disease (IBD) encompasses two distinct diseases: Crohn’s Disease (CD) and Ulcerative Colitis (UC). Mucosal healing is the preferred treatment target, as patients who achieve mucosal healing have improved outcomes, including decreased risk of surgery, and lower relapse rates. However, almost all therapies are given either orally or intravenously resulting in non-target systemic distribution with only minimal therapy reaching the bowel. Our research focuses on delivering MSC therapies directly into the arterial circulation of the bowel to ensure their maximal therapeutic efficiency at inflamed segments to thereby improve their therapeutic effects.

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Alzheimer’s Disease (AD) is a neurodegenerative disease and the leading cause of age-associated dementia. Although the mechanism underlying the pathogenesis of AD still remains elusive, a large body of evidence suggests that damaged mitochondria play a fundamental role in both neurons and microglia in the hippocampus. Our research focuses on locoregional delivery of MSC therapies with a high bioenergetic cargo directly into the blood vessels which supply the brain as well as modulating the blood-brain barrier through soundwave modulation.

Pancreatic Cancer is a lethal malignancy with a very poor survival rate. Systemic intravenous chemotherapy administration is the first-line treatment for patients with unresectable pancreatic cancer; however, its responses are limited given issues related to limited drug concentration reaching the tumor, systemic toxicity and poor tumor penetrance. Our research aims to improve the effects of chemotherapy by administering it directly into pancreatic tumors, via its arterial blood supply, as well as modulating the stomal barrier surrounding the tumor using soundwaves.

Bioscaffolds are platforms that can accommodate cell cargos which can then be implanted into patients. Our research has been developing novel bioscaffolds that can accommodate different cell therapies while also inducing minimal soft tissue and fibrotic responses. These bioscaffolds can also be specifically functionalized to allow them to reenergize and protect cell cargos as well as provide them with nutrients and oxygen while they engraft and get vascularized for long term autonomous function.

Precision Equipment are essential to accomplish precision delivery in patients. We work closely with main stream imaging vendors to optimize equipment that help us “see-inside” and intervene upon the human body; start-ups and device manufacturers to develop new catheters and devices for drug and cell delivery; and even developing new devices in our own lab for children given their unique smaller body size and continual growth trajectory; indeed, we envisage one day of being able to develop “custom devices”, specific for individual patients, using advances in technologies like 3D printing..

Diabetes

Acute Kidney Injury

Alzheimer's Disease

Acute Respiratory Distress Syndrome

Inflammatory Bowel Disease

Pancreatic Cancer

Bioscaffolds

Precision Equipment

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