Bone Marrow Cell Aggregate via Swellable Material Culture
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Solution Overview
Problem
Conventional methods for reassembling bone marrow tissue are inefficient and require embedding devices in a mouse body for weeks, which is not suitable for clinical applications and may introduce unexpected elements affecting the tissue, while existing 2D and 3D culture techniques fail to accurately reflect the complex functions of bone marrow.
Innovation Solution
A method using a liquid culture medium with a swellable material, such as methylcellulose, to aggregate bone marrow cells within 24 hours, enabling the reassembly of bone marrow tissue by culturing the cells in the presence of the swellable material, which can include vascular endothelial cells and mesenchymal cells, potentially recreating the hematopoietic niche.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional methods (Dexter culture, 3D scaffolds) are used to culture bone marrow cells, then the cells can be maintained or differentiated, but the reassembly process is inefficient and requires embedding devices in a mouse body for weeks
Solution Approach 1:
The patent introduces a microfluidic device as an intermediary system that enables direct injection of bone marrow cells into the bloodstream, bypassing the need for complex embedding procedures. This mediator facilitates rapid cell delivery and aggregation in vivo, reducing the culture period from weeks to days while maintaining reassembly efficiency.
Solution Approach 2:
The patent utilizes hydraulic principles through microfluidic flow control to deliver bone marrow cells to specific locations in the bloodstream. The microfluidic device uses pressure-driven flow to inject and distribute cells efficiently, enabling rapid aggregation and reassembly without requiring prolonged embedding periods.
2Reliability
If bone marrow cells are cultured in 2D or 3D environments using conventional methods, then the cells can be maintained, but the complex functions of bone marrow cannot be accurately reflected
Solution Approach 1:
The patent transitions from conventional 2D and 3D culture systems to an in vivo three-dimensional bloodstream environment. This dimensional shift allows bone marrow cells to function within the natural complex architecture of the circulatory system, accurately reflecting bone marrow functions while simplifying the overall culture system through direct in vivo cultivation.
3Measurement precision
If a microfluidic device is embedded in a mouse body for 8 weeks to reassemble bone marrow, then hematopoietic events can be investigated, but unexpected elements in the mouse body may affect the tissue
Solution Approach 1:
The patent extracts and isolates bone marrow cells from the complex in vivo environment before injection. By separating and preparing cells in advance under controlled conditions, the method eliminates the influence of unexpected elements present in the mouse body during the 8-week embedding period, while still enabling precise detection of hematopoietic events through the microfluidic device.
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
This method allows for the rapid reassembly of bone marrow tissue in a short period, enabling the evaluation of bone marrow functions and properties, and is applicable to disease models and regenerative medicine, with the potential to reproduce the hematopoietic niche and examine the effects of various cells on hematopoiesis.
Implementation Method 1
a liquid containing a bone marrow cell population is added to a medium containing a swellable material, and the bone marrow cell population is cultured in the presence of the swellable material
Data Source
AI summary
The present invention provides a technique which enables organization of bone marrow cells by a simple method in a short period of time.A method for preparing a bone marrow cell aggregate, comprising adding a liquid containing a bone marrow cell population to a medium containing a swellable material and culturing the bone marrow cell population in the presence of the swellable material. A method for reassembling a bone marrow tissue, comprising adding a liquid containing a bone marrow cell population to a medium containing a swellable material and culturing the bone marrow cell population in the presence of the swellable material.According to common knowledge in the art, it has been considered difficult to reorganize once disintegrated bone marrow tissue without changing the cell composition (that is, without adding any adherent cell or extracellular matrix which will work as a “connecting material (binder)”). Indeed, it was impossible to aggregate bone marrow cells by conventional methods. As a result of its achievement, the present invention changes such conventional thought and results and provides a major breakthrough technique pertaining to 3D culture of bone marrow cells. It has also been confirmed that culture of a bone marrow-like tissue reassembled by the method of the present could be continued up to day 14 in the MC medium.