Abs Khan

#organoids #organ-on-chip #myeloma #NAMs #myeloma @imm.ox.ac.uk

If you (like us) are a bone marrow and human pre-clinical modelling enthusiast, do join our google group : (groups.google.com/g/morerganoids)

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

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.

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.

8 years of funding is an incredible opportunity to get stuck in so very excited to get cracking with some research!

A huge and heartfelt thank you to all the wonderful colleagues and friends who have supported me through the highs and lows to get here. There are too many to name (and I'd be afraid to miss someone)... but none of this is possible without people fighting your corner.

!!! It's official !!

After a very, very long couple of years of rejections and the seemingly impossible task of juggling grant writing with bench work, supervision, admin, paper writing.. very happy to officially start as a @wellcometrust.bsky.social funded group leader at the WIMM

Body-in-a-chip approach reveals how immune cells respond to heart injury Oxford scientists build a connected, ‘multi-organoid’ platform that recreates immune recruitment to the heart, opening new avenues to probe disease and test therapies.

NEW: Oxford researchers link mini organs to show how immune cells race to the rescue after heart injury 🧪

@abattacks.bsky.social & colleagues linked cardiac and bone marrow organoids with a 3D-printed device to model this complex immune response.

Learn more 👇

@rdm.ox.ac.uk | @medsci.ox.ac.uk

As a side note - I didn't think much of a 100km row over the whole month, but 10km in and I must say I am questioning my judgement/fitness/ability...

HSCB lab rows 100km each for bone cancer research Help Abdullah Khan raise money to support Bone Cancer Research Trust

Different flavour of post from me today!

A bunch of us in the lab at the @imm.ox.ac.uk are taking up Bone Cancer Research Trust (BCRT)'s June rowing challenge to both raise funds and awareness:

www.justgiving.com/fundraising/...

Please share/donate if you can!

Looking forward to it Zoltan - bring me some home cooking !

I loved this course! If Aiden or Natalie are instructing say hi from me!

Thank you 😀

😊🥹

🔥 New Fraticelli lab publication🔥

“Pre-existing stem cell heterogeneity dictates clonal responses to the acquisition of leukemia driver mutations”

Now at Cell Stem Cell, with two new figures, in vivo, and sequential mutagenesis data.

Performed with the support of Cris Cancer and @erc.europa.eu

Very kind of you Dianne, appreciated!

Finally finally a big thank you to everyone who has engaged with and showed an interest in implementing the system. I am hopeful that we can make big strides forward as a community as these types of systems advance. Thank you to patients + funders!

. If you're interested in implementing please join: groups.google.com/g/morerganoids
Where we help troubleshoot + share protocols etc.

And this is the playlist:
open.spotify.com/playlist/380...
To which the paper was written for everyone out there who writes/works to very specific music.

A lot of the major therapeutic challenges and many interesting questions are around clonal evolution, chemoresistance etc. To address those well we need longer lived, 'stable' cultures - we see a decline in complexity over time in our static cultures. Watch this space!

I'll end on quoting @kellystevens.bsky.social 'It's not about how far we've come, but about how far we have left to go.' I hope you will agree this is a big step forward, but there are still challenges that I am excited to tackle (funding pending of course).

... you can build in a lot of complexity and work out strategies to retain throughput and scalability.

We present what we believe is a highly complex in vitro model that showcases the potential of human organoid systems. By adapting granular microgels pioneered by colleagues in the bioengineering field (e.g. J Burdick and others), I think we also show that...

Finally that helps us identify an inflammatory pathway (MIF) which we think underpins myeloma mediated inflammation. We show that inhibiting this in myeloma-comBO chimeroids ameliorates markers of inflammation.

We then apply this system as a pre-clinical model to study multiple myeloma - showing that we support primary myeloma cells (notoriously difficult to culture ex vivo) and capture hallmarks of their extensive interactions with bone marrow niches.

In this manuscript we address these to present comBO: a combined bone and lympho-myeloid bone marrow organoid system (I know the acronym is a bit of a reach, but it's stuck now).