Pfeifer1982.
One of the reasons it took a day for me to write such a rushed previous post ( apologies that it repeated itself in parts and some of the jokes fell flat), is that I did not want to be dogmatic or partisan in my view of Mesoblast. I read all of your posts since August of this year and all the links you referred to. I can see you have good reason to be excited by Cynata but in all your excitement you have overstepped the mark by jumping to conclusions about MSB which you then post on this thread. I do accept that HotCopper exists to encourage debate and that you have been meticulous to reference your sources, which allows independent thinkers to evaluate further...but with current market conditions, your negative conclusions would have only added to the share price malaise being caused by market conditions and the bears who have built up a short position of 7.55% making MSB about the 15th most shorted stock on the ASX . Although much of my post was tongue in cheek with some Christmas spirit underlying I was trying to make some serious points.
1) Industry first undertakes clinical research and then scales up the manufacturing process. What it does not do is make fundamental design changes during a regulatory evaluation.
This does not mean that a process of continuous improvement is not being undertaken from both within and outside the Company by its supply chain. If that progress is accepted by the FDA it might be incorporated into an existing application. We will have to wait to see what changes (if any) they have made to the existing manufacting process which is subject to current trials. I made the point that these advances or a change in harvesting methods could be applied to future treatments. You quote yields from 2017, blissfully unaware that 3D bioreactor yields have recently improved substantially. Cell potency and activity has been improved by technology which reduces damage from the production process such as the "shear effect" . Structural scaffolds make more efficient use of serum which is the biggest consumable. Productivity yields from a 50L bioreactor have now achieved a 43 fold increase not the 20 times you refer to....and that was peer reviewed research from August 2018...much has happened since then.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931275/
Published studies of bioreactor cultures of mesenchymal- and adipose-derived stem cells typically report data for bioreactors with maximum volumes of 3 L 11, 12, although Lawson et al. demonstrated the ability of these systems to safely and effectively enable a 43-fold cell expansion over 11 days using a 50 L volume bioreactor with a graduated agitation and feeding scheme 11. The cells retained their tri-lineage pluripotency, T-cell modulation behavior, and phenotypic markers, including CD44 and CD90, when compared with cells cultured under traditional conditions 11. However, these studies used growth factors and animal serum in their media. The development of defined media without supraphysiological concentrations of growth factors in cell culture would promote economically feasible industrial-scale culture. Another key shortcoming is the dearth of in vivo efficacy data from cells produced in these large-scale bioreactors.
Please also note that the yield and potency improves which would theoretically suggest that lower dosages would be required to achieve the same effect. By the way you make take comfort from the same article which validates the potential of next gen cell replication methods for iPS.
Induced pluripotent stem cell expansion
Using this continuous expansion method in a stirred-tank bioreactor, Abecasis et al. demonstrated 1,100-fold expansion in 11 days using 4% dissolved oxygen 25. The resulting cells were characterized by using proteomic and gene stability analysis as well as proliferation and gene expression assays to validate their naïve state
The reason why SI does not want to reveal too much is obviously commercial sensitivity. If you do not accept this, then consider why have recent partnership deals have been signed with milestones paid for a technology which is uneconomic to produce...I don't think so.
Much more progress to come
Thanks to NASA we now have organoid technology operating in low media conditions etc.
http://sci.amegroups.com/article/view/21769/21219
The improved organization and behavior of cells in bioreactor-cultured retinal organoids was evident in several recent studies involving an array of tissue types (12,13). However, many modern bioreactors are quite large; their prolonged used is frequently cost-prohibitive, potentially consuming liters of expensive growth factor-containing medium during a single experiment. A traditional perfusion RWV and a stirred-tank bioreactor may each hold up to 100 mL. The entirety of the media may need to be changed between each stage of differentiation, rapidly escalating the cost. Additionally, bioreactors are often not purpose-built for specific organ-type applications and are frequently skill- and experience- limiting. Until recently, researchers had endeavored to optimize bioreactors for 3D tissue culture (14,15) but were limited due to availability of differentiation protocols and advanced fabrication techniques. In the new era of 3D printing and mass customization, new generations of bioreactors are being developed that offer optimized organoid culture at reduced cost and improved reproducibility.
Don't worry I believe iPS
will be an improvement, but I can safely say that t
he historic yields
being used in your calculations are incorrect in relation to both yields and potency which has a bearing both dosage requirements and clinical outcomes.
Merry Christmas
P.S. I did mark your post up. A for effort and enthuisiasm.
(20min delay)