A number of in vitro systems have been developed in which two or more different cell types are cultured together to more closely replicate the environment of the in vivo niche of the test cells than culturing the cells in isolation can provide. ReachBio Research Labs’ scientists have experience in using a variety of primary cell and cell-line co-culture systems to test the effects of test compounds on certain cell types.
Examples of Co-Culture Systems we Employ Include:
Long Term Bone Marrow Cultures were first described by Dexter et al. These co-culture systems allow for the continuous culture of bone marrow hematopoietic cells on an adherent layer of bone marrow stromal cells. Within this in vitro culture system, hematopoietic stem cells retain their “stemness” in that they continuously generate the various progenitors and mature progeny of multiple blood cell lineages and also can reconstitute the ablated hematopoietic system of irradiated mice. The progenitor cells generated in this system can be quantified and evaluated using colony-forming cell assays.
The Long Term Bone Marrow Culture system allows the continuous administration of test compounds and kinetic evaluation of their impact on hematopoietic stem cells and progenitor cells.
Evaluation of the ability of normal and diseased marrow stroma to support hematopoietic stem cell function.
Certain leukemic cell types (e.g., Multiple Myeloma, ALL, etc.) can be cultured on an adherent layer of bone marrow stromal cells. This creates an environment closer to the in vivo “bone marrow niche” than simply culturing the cells on their own. In certain situation, the stromal cells may provide the leukemic cells a degree of protection from therapeutic agents. This type of in vitro co-culture system can therefore be used in addition to leukemic CFC assays to provide more insight about the effects of test compounds on leukemic progenitor cells.
Certain biologics can trigger massive cytokine release from lymphocytes, resulting in a potentially deadly cytokine storm in vivo. Testing of biologics for this type of risk usually requires cross-linking of the test compound in some way in order for the lymphocyte to be activated. In simple in vitro systems where the lymphocytes / PBMCs are cultured alone, this cross linking is done in an artificial way such as imobilization on plastic culture dishes or the addition of anti-Ig cross linkers. By co-culturing PBMCs with an adherent layer of HUVEC cells, a more natural environment is created and the interaction of the different cell types allows for signal transduction to be induced by the test biologic without the need for artificial cross linking to be applied. This has the advantage of being able to test the biologic in a natural, soluble conformation and also allows for a more accurate and quantitative dose response.
For more information, please see our Cytokine Storm Risk Analysis page.
Evaluate and rank the ability of your candidates to recruit T cells and NK cells to kill cancer cells
- In vitro antibody-dependent cellular cytotoxicity (ADCC) assays
- Compatible with bi-specific antibodies and other immune cell recruiters
- Measure primary immune cell killing of target cells
- Flow cytometry-based readout with additional intracellular analysis, if desired
- Customized to your program’s needs