Selective cytopheresis devices and related methods thereof
Inventors
Humes, H. David • Buffington, Deborah
Assignees
University of Michigan Ann Arbor • Seastar Medical Inc
Publication Number
US-9128093-B2
Publication Date
2015-09-08
Expiration Date
2028-08-29
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Abstract
The present invention relates to systems and devices to treat and/or prevent inflammatory conditions within a subject and to related methods. More particularly, the invention relates to systems, devices, and related methods that sequester leukocytes and/or platelets and then inhibit their inflammatory action.
Core Innovation
The present invention provides systems, devices, and methods for treating or preventing inflammatory conditions in a subject by extracorporeally sequestering leukocytes and/or platelets and subsequently inhibiting or deactivating their inflammatory action. The process involves associating these cells with a device surface—such as the exterior of hollow fibers—followed by exposure to an agent, often a calcium chelating agent like citrate, which reduces the cells' ability to release pro-inflammatory substances.
The invention addresses the problem of unwanted and potentially fatal inflammation within the body, particularly as caused or exacerbated by activated leukocytes and platelets. Such inflammation contributes to conditions including systemic inflammatory response syndrome (SIRS), sepsis, ischemia/reperfusion injury, and acute respiratory distress syndrome (ARDS), where abnormal or excessive immune cell activation leads to tissue damage and organ dysfunction.
The core method of the invention involves flowing a biological sample, such as blood, through an extracorporeal circuit containing at least one selective cytopheresis inhibitory device (SCID). Leukocytes or platelets are sequestered via interactions with device surfaces under low shear force conditions, allowing efficient binding. Subsequent treatment with an agent—preferably a calcium chelator—deactivates the inflammatory activity of these sequestered cells before returning the processed blood or fluid to the subject. This approach has shown significant benefit in reducing inflammatory responses and improving survival in both preclinical animal models and human studies.
Claims Coverage
There are two independent claims, each focusing on methods involving sequestration and treatment of leukocytes with a calcium chelating agent for subjects with ALI or ARDS.
Method for processing a leukocyte from a subject with ALI or ARDS by sequestration and treatment with a calcium chelating agent
This inventive feature includes: - Extracorporeal sequestration of a primed or activated leukocyte from a body fluid of a subject diagnosed with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). - Application of a calcium chelating agent to the sequestered leukocyte to inhibit the release of a pro-inflammatory substance or to deactivate the leukocyte. - The calcium chelating agent may be provided in the passageway where sequestration occurs, and may be infused during the process. - The exposure duration to the chelating agent can range from less than an hour to up to 24 hours, with sequestration for at least one hour as preferred in some embodiments. - The sequestration region comprises a membrane, preferably porous and with a surface area greater than about 0.2 m², configured for low shear force (less than about 1000 dynes/cm², or preferably less than 100 dynes/cm² at flow rates of around 100–500 mL/min). - Citrate is a preferred calcium chelating agent, and after processing, the treated leukocyte may be returned to the subject.
Method for treating inflammation in a subject with ALI or ARDS by sequestration and treatment of leukocytes with a calcium chelating agent
This inventive feature includes: - A method for treating inflammation in a subject with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). - Sequestration of a primed or activated leukocyte extracorporeally from a body fluid of the subject. - Treatment of the sequestered leukocyte with a calcium chelating agent, such as citrate, to inhibit the release of a pro-inflammatory substance from the leukocyte or to deactivate the leukocyte, thereby treating inflammation in the subject. - The process may be conducted in a device having a passageway region with a membrane (porous and with a surface area greater than about 0.2 m²) where low shear force facilitates binding of leukocytes. - The calcium chelating agent is supplied in the passageway, and the leukocyte may be exposed for less than an hour or from 1 to 24 hours before returning to the subject.
Both independent claims protect methods that combine sequestration of activated or primed leukocytes and subsequent treatment with a calcium chelating agent, specifically targeting inflammatory conditions such as ALI and ARDS, using specialized extracorporeal devices and specified process parameters.
Stated Advantages
The systems, devices, and methods of the invention provide unprecedented and surprising success in maximizing subject survival during treatment of inflammatory diseases and conditions.
The invention enables efficient sequestration and deactivation of inflammatory leukocytes and platelets, reducing multi-organ effects of inflammatory diseases.
Using a calcium chelating agent like citrate results in decreased release of inflammatory mediators from leukocytes and leads to amelioration of the inflammatory state.
The invention can be implemented with existing dialysis equipment, allowing broader and simpler clinical adoption.
Treatment according to the invention shows improved cardiovascular performance and survival outcomes in both animal and human models compared to controls.
Leukocyte deactivation and inhibition is achieved without the need for systemic administration of expensive or immunosuppressive drugs.
Documented Applications
Treatment and/or prevention of inflammatory conditions such as systemic inflammatory response syndrome (SIRS), sepsis, acute respiratory distress syndrome (ARDS), cardiopulmonary bypass syndrome, rheumatoid arthritis, systemic lupus erythematosis, inflammatory bowel disease, multiple sclerosis, psoriasis, allograft rejection, asthma, chronic renal failure, cardiorenal syndrome, hepatorenal syndrome, acute organ failure due to ischemic reperfusion injury, and acute organ failure due to toxic injury.
Treatment of inflammation in subjects with acute lung injury (ALI) or ARDS by extracorporeal processing and return of deactivated leukocytes.
Applications in cardiopulmonary bypass (CPB) circuits to sequester leukocytes and platelets, minimize CPB-induced acute lung and kidney injury, and improve clinical outcomes during and after surgery.
Use with subjects having end stage renal disease (ESRD) to treat chronic pro-inflammatory states and reduce mortality risk associated with cardiovascular disease and infection.
Support of organ harvesting for transplantation, tissue engineering, ex vivo generation of organs, and manufacture and use of bio-micro electromechanical systems (MEMs).
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