Stem cells ramping up.., page-35

Because the senseless discussion about MSB vs CYP is starting to get annoying i will try to give a new twist to the situation.

Let me ask you guys one question: what is the therapeutic entity that MSB, CYP, RGS and many other regenerative medicine companies are using?

 Yes i assume everyone guessed it right its mesenchymal stem cells (MSC)!

Because at this point in time there is NO MSC based therapy approved for the treatment of any condition globally, I have to say that each an every single Phase 1/2/3 study that uses MSCs and shows clinical effectiveness is a validation that I as a investor in a regenerative medicine company, working on the development and commercialisation of MSC products (yes that can either be MSB or CYP or any other company), have put my money on a the yet unproven therapeutic entity (MSCs) that rapidly accumulates data showing that it is a highly effective treatment option for a variety of unmet diseases. Therefore, the continues success of MSCs in clinical trials is de-risking my investment regardless of the individual company.

Beyond the general positive implications of the success of MSB and CYP for the general regenerative medicine field each company has its own advantages.

CYP has the advantage that they dont have to continuously get new donors, no question about that. 

MSB has the advantage of being the front runner, and MSB will enjoy a few years without competition, no question about that. If anyone thinks (as partially suggested in some previous posts) that the FDA, big pharma or the people will ignore MSC treatments and wait for CYP to get there they are disillusional.

However a advantage that is absolutely overstated by many CYP posters is that irrespective of where you get your MSCs from, the expensive aspect of the manufacturing process is the expansion, specifically the cell culture medium. And in that regard 3D bioreactors are the future. Any company developing cell based medicines have to maximise the cells/mL media. This might be more important for CYP because they have the additional step of differentiating iPSCs to mesenchymoangioblast (MCA) by adding serum-free clonogenic medium with FGF2, before they can generate MSCs (DOI 10.1016/j.stem.2010.11.011 original publication of Prof Slukvin).

The question is how the expenses of this additional step compares to sourcing multiple donors. Most likely it will still be cheaper i assume but its definitely something that has to be considered. 

As an example for 2D vs 3D expansion methods:

A study expanding UCM sourced MSCs  using a 10-layer HYPER flasks (Corning) (traditional 2D culture method) and 560mL of α-MEM + 15% AB human serum media received 45 × 10⁶ cells or 80 x 10³ cells/mL medium used

Another study again expanding UCM sourced MSCs in a fixed-bed bioreactor (New Brunswich) and 500mL of α-MEM + 10% FBS media received 420 × 10⁶ cells or 920 x 10³ cells/mL medium used. 

Reference and in general a interesting read about MSC manufacturing https://doi.org/10.1155/2018/4083921.

Please note that the above example use different serum which can influence the growth  and I am not sure about the starting cell number in the individual study. The point of the given example is to showcase the potential differences of cells/mL media of the different expansion strategies. The limiting factor for 2D is the surface area of the dishes, which will always be much worse than 3D bioreactors.

Both MSB and CYP will have to do the QC to ensure batch to batch consistency (MSB) and successful and complete differentiation (CYP, you definitely dont want residual iPSCs in your therapeutic product and induce teratomas in the patients) so that aspect should be equal.

Overall the manufacturing advantage of CYP to produce consistent and possibly more effective (less propagated) MSCs stands against the huge IP advantage of MSB, while both companies will need to develop 3D bioreactor based expansion methods to truly produce cell numbers that are able to satisfy one or multiple of the huge global market opportunities like OA, CHF, CLBP ect. 

I already asked that question before without an answer so i will ask again, may any of the CYP investors comment on the fact that MSB has many patents with the intention to tread different diseases using MSCs. How will that affect CYP? Because in both cases the therapeutic entity are MSCs it looks like MSB will enjoy no competition for a few years anyway no?