Lymphoid Tissue-Derived Suppressive Stromal Cells for Autoimmune Therapy
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Solution Overview
Problem
Current immunosuppressive drugs for treating autoimmune and inflammatory diseases are often ineffective and carry significant side effects, and the isolation of stromal cells for therapeutic use is challenging due to their poor definition and difficulty in successful isolation.
Innovation Solution
Isolation and ex vivo expansion of lymphoid tissue-derived suppressive stromal cells (LSSC) from tissues like lymph nodes, which can suppress immune responses by attracting and inhibiting immune cells, offering a novel therapeutic approach for autoimmune and inflammatory diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional immunosuppressive drugs are used to treat autoimmune and inflammatory diseases, then immune system activity is inhibited, but significant side effects including renal toxicity and morbidity occur
Solution Approach 1:
The patent extracts and isolates specific suppressive stromal cells (SSC) from lymphoid tissues to create a targeted cell-based therapy. This extraction approach separates the therapeutic immunosuppressive function from the harmful side effects of conventional drugs, as the isolated cells can be administered at controlled doses (e.g., at least 0.1 million LSSC/kg) to achieve immune suppression without the systemic toxicity of traditional immunosuppressive drugs.
Solution Approach 2:
The suppressive stromal cells act as intermediary agents that mediate immune suppression through cell-to-cell interactions and secretion of regulatory molecules. These cells serve as a biological mediator between the administered therapy and the immune system, providing controlled suppression through mechanisms such as T cell inhibition and cytokine modulation, rather than direct pharmacological suppression that causes tissue damage.
2Ease of manufacture
If stromal cells are isolated for therapeutic use, then a cell-based immunosuppressive therapy can be provided, but isolation remains challenging due to difficulties in successfully isolating these cells
Solution Approach 1:
The patent segments the complex isolation process into distinct sequential steps: (i) incubating lymphoid tissue fragments with enzyme mix, (ii) agitating the tissue using a pipette followed by incubation to allow large fragments to settle, (iii) removing the supernatant and repeating steps (i) and (ii) until all fragments are digested. This segmentation transforms a difficult single-step isolation into a manageable multi-step protocol with clear endpoints, enabling successful isolation of suppressive stromal cells.
Solution Approach 2:
The isolation methodology employs dynamic mechanical agitation using a pipette followed by static incubation periods to allow fragments to settle. This dynamic-static cycle is repeated until complete digestion is achieved, creating a flexible adaptive protocol that can be adjusted based on tissue type and fragment size, thereby overcoming the rigidity and difficulty of conventional isolation methods.
3Adaptability or versatility
If immunosuppressive stromal cell types are used in clinical trials, then a biological therapy approach is provided, but they have failed to meet primary efficacy endpoints due to being poorly defined
Solution Approach 1:
The patent replaces conventional mechanical and chemical isolation methods with a defined enzymatic digestion system using specific enzyme mixes. This substitution provides precise control over the isolation process, enabling consistent recovery of suppressive stromal cells with defined characteristics (e.g., CD45-negative, CD271-positive phenotyping). The enzymatic approach allows for reproducible isolation that meets manufacturing precision requirements, unlike previous poorly defined methods that failed in clinical trials.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
LSSC effectively suppress immune responses, providing a promising treatment for conditions such as rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease with reduced side effects compared to traditional immunosuppressive drugs.
Implementation Method 1
digesting lymphoid tissue fragments using a combination of an enzyme mix and agitation
Implementation Method 2
The LSSC are collected by pooling all supernatant fractions followed by centrifugation to obtain cell pellets
Data Source
AI summary
A method for suppressing an immune response is provided. The method involves administration of isolated lymphoid tissue-derived suppressive stromal cells (LSSC) to a subject in need of such treatment in an amount effective to suppress the immune response in the subject. The invention also involves a method to isolate LSSC by digesting lymphoid tissue fragments using a combination of an enzyme mix and agitation and then collecting the LSSC. Pharmaceutical preparations comprising LSSC are also provided.