Another step on the journey towards building human bone marrow in vitro:
doi.org/10.1016/j.st...
When we published our first version a few years ago (doi.org/10.1158/2159...) the glaring gap was the lack of mature osteolineage (bone forming) cells, adipocytes, and lymphoid cells.
We have a lot of exciting new stuff coming - so watch this space! Including expanded implementations of comBO in multi-organoid, ‘body-in-a-dish’ approaches (teaser here: www.ahajournals.org/doi/10.1161/...).
We go on to show that myeloma cells, notoriously difficult to culture in a dish, not only survive but proliferate and expand in comBOs. This enables effective pre-clinical modelling, and identifies a tractable pathway linking tumour growth and inflammatory remodelling of the TME.
Importantly, this complexity is achieved without bulk hydrogels — enabling scalable and automatable workflows. This is critical for effective pre-clinical modelling and discovery research.
In this work, we close that gap.
comBOs are derived from a handful of induced pluripotent stem cells (iPSCs) and develop into a multilineage haematopoietic and stromal organoid which closely resembles adult bone marrow (as benchmarked by single-cell transcriptomics against adult human bone marrow).
Recent papers have tackled aspects of maturing bone marrow organoids (BMOs), but the challenge has been building a single model that captures all these cell types. Without these lineages in a single system, key niche interactions that regulate haematopoiesis can't be faithfully modelled.
A huge thank you to everyone involved (too many to call out individually), in particular @yuqi-shen.bsky.social – it’s been a lot of work getting this together, and it’s been fun having such a wonderful partner in crime. Also big thank you to @Sarah gooding for all her guidance on all things myeloma
Abs Khan
If you (like us) are a bone marrow and human pre-clinical modelling enthusiast, do join our google group : (groups.google.com/g/morerganoids)
