Allogeneic MSCs
The question: is allogeneic stem cell treatment a better option than autologous?
Does allogeneic “work” regardless of the mechanism?
Does it work as well as autologous?
Do the cells work via paracrine only, or are they able to differentiate and engraft?
Human orthopedic clinical studies
Iran 2018
Average passage 12 (!!!)
10mL injectate
0.5 x 10^8 = 50,000,000
Placental cells
N = 20
Results
No improvement in VAS
KOOS scores did improve significantly. But this is complex.
ADL and QOL improved up to 8 weeks
“Symptoms” improved up to 8 weeks, but deteriorated between 8 and 24 weeks such that there was no improvement at 24 weeks.
Chondral thickness increased in 10% of regions measured
ROM increased by much more in the treatment group.
The data is not given in the study.
The study demonstrated safety, but not efficacy very convincingly.
2018, Chile
N = 29, divided into 3 groups
HA, 1 x 20M, 2 x 20M (six months apart)
Injectate 3cc
20M WJ cells intra-articular
Double blind
Assessed at intervals up to 52 weeks
Results
WOMAC
All 3 groups improved.
MSC-1 didn’t fare much better than the placebo group.
MSC-2 did much better than both groups
VAS
All 3 groups improved
MSC-1 did significantly better than HA group
MSC-2 did significantly better than both groups
OMERACT‐OARSI
MSC-1 group did well at 24 weeks, but backslid at 9 months, and by 52 weeks was even with HA group
MSC-2 group did exceedingly well at 52 weeks
WORMS
There were no radiological improvements in any group
100% of MSC-2 PATIENTS WERE RESPONDERS.
2020, Indonesia
N = 29
hUC-MSCs + HA
10 x 10^6 = 10M cells, 2mL injectate
Followed up by three HA injections
NOT RANDOMIZED, NO CONTROL
Measured outcome at 6 and 12 months with VAS, WOMAC, IKDC, and MRI
Outcomes
Clinical outcomes:
Definite improvement
Subjects achieved maximum improvement at 6 months, and held improvements at 12 months
MRI:
T2 mapping = measures fluid volume of cartilage
T2 decrease = more water = good
In the mild group, T2 improved at 6 months in the medial compartment, but regressed by 12 months, and the final scores were worse than baseline.
In the severe group, mean T2 saw massive improvements at 6 months, and subjects continued improving dramatically through 12 months. Median scores peaked at 6 months, but subjects held improvements at 12 months.
Treatment of Knee Osteoarthritis With Allogeneic Bone Marrow Mesenchymal Stem Cells
Transplant Direct. 2017 Sep (Spain)
Human study on allogeneic BM
N = 30 RCT allo BM vs HA
40 × 10^ 6 = 40M cells
Improved cartilage quality
This is allogeneic BM, not WJ.
Cartistem
Published 2020
This is not intra-articular injection, but arthroscopic surgery.
Involved debrision, creating a large defect with the bone exposed. They drilled holes, and implanting a mix of HA and hUCB-MSCs into the defect
N = 128
2 year followup
Cartilage regeneration and improves VAS and WOMAC scores
Unknown what influence the drilling played.
a Clinical Trial for Safety and Proof-ofConcept With 7 Years of Extended Follow-U
2017
N = 7
“Cartistem”
Grade 3 and 4 cartilage lesions.
The lesions were debrided, and the bone was exposed and drilled.
This was not an IA injection, but an arthroscopic surgery.
Regeneration of hyaline-like cartilage observed
Intervertebral Disc Repair by Allogeneic Mesenchymal Bone Marrow Cells
Sept 2017
Studied allogeneic BM-MSCs in both discs and knees
Immune activity “weak and transient”
HLA matching does not enhance the efficacy of the treatment.
Reviews
Mesenchymal stem cells and immunomodulation: current status and future prospects
Progress in the treatment of osteoarthritis with umbilical cord stem cells
Mesenchymal stem cells: immune evasive, not immune privileged
This paper argues that allo MSCs are NOT immune privileged, but doesn’t mention Wharton’s Jelly.
Claims WJ-MSCs are different from AD and BM-MSCs in terms of immunogenicity.
At this time, no definitive recommendations can be made regarding which MSC source to use. Allogeneic MSCs offer theoretical advantages over autologous MSCs, especially in ease of use and consistency of product, but there are concerns regarding cell viability and vitality, as well as the body’s response to nonautologous products.
Progress in the treatment of osteoarthritis with umbilical cord stem cells
WJ low immunogenicity compared to BM and adipose
Dr. Centeno blog entries (chrono order)
Stem Cell Treatment Side Effects: IV Umbilical Cord Risks (8/12/19, 7/23/21)
The Regen Med Research Has a Dirty Little Rat Secret (2/7/20, 7/17/21)
The Stem Cells in a Vial Model for Arthritis May Not Be Viable (3/7/18, 7/17/21)
What happens to the Stem Cells when you Get Someone Else’s Cells? (10/30/13) 1/24/20)
Genes of donor stem cells stay working in the host
“Allogeneic mesenchymal stem cell (MSC) transplantation improves cardiac function, but cellular differentiation results in loss of immunoprivilege and rejection. “
Why are we considering the use of other peoples stem cells for treatment? (4/20/2009, 1/24/20)
Osiris pulled Prochymal because the trial failed.
“...several studies have shown that the body does recognize these cells as foreign, but through a different mechanism than was first considered (killer T-cell system). So in my opinion, the lack of efficacy for both Prochymal and Chondrogen for Osiris is most likely related to the cells being taken out (killed off) by the host’s immune system.”
What Are the Bioethics of Sourcing Birth Tissues and Selling Them for Huge Money?
Cites study: autologous BM-MSCs differentiate and engraft into disc material.
Opines that in his educated opinion, autologous MSCs differentiate, while allogeneic work by paracrine only.
Points to equine study showing that the animal’s immune system destroyed non-HLA matched BM-MSCs
“Using someone else’s MSCs has a built-in problem. Why? On the one hand, we know that they are immunoevasive, which means that they can evade the host’s immune system and become invisible to the main immune response. On the other, eventually, they get taken out by the killer T response from the host’s immune system. This is different than your own MSCs which stick around.”
