Marc Darrow MD, JD. Thank you for reading my article. You can ask me your questions using the contact form below. 

Stem cell therapy works in a multi-factorial way. Stem cells repair, stem cells regenerate, and stem cells communicate. Communication is one of the key but less understood functions of stem cell therapy. In this communication aspect, newly introduced stem cells (injections) mobilize stem cells already in your knee to jump start a new repair cycle for degenerative and acute injury damage. But many patients, especially older patients, question whether they have enough of their own stem cells to heal. Researchers are saying. Yes. But you need new stem cells to tell the old ones what to do.This is called “Cell SIgnalling.”

If you are someone questioning the numbers of stem cells, let’s look at nearly a decade’s worth of research.

In 2011, doctors at the University of Aberdeen published research in the journal Arthritis and rheumatism that provided the first evidence that resident stem cells in the knee joint synovium underwent proliferation (multiplied) and chondrogenic differentiation (made themselves into cartilage cells) following injury.(1)This paper, presenting the idea that stem cells in an injured knee increased in numbers in preparation of healing has been cited by more than 55 medical studies.

The most recent of these 55 papers is a June 2019 study (2) in which researchers suggest that in both rheumatoid arthritis and degenerative arthritis, communications between cells increase cell numbers in a damaged knee.

If the stem cells in your knee’s synovial lining are abundant and have the ability to rebuild cartilage after injury, why isn’t your knee fixing itself?

Another of those 55 studies was performed by researchers at the University of Calgary in 2012. Among their questions, if the stem cells in the knee synovial lining are abundant and have the ability to rebuild cartilage after injury, why isn’t the knee fixing itself? Here is what the researchers published:

“Since osteoarthritis leads to a progressive loss of cartilage and synovial progenitors (rebuilding) cells have the potential to contribute to articular cartilage repair, the inability of osteoarthritis synovial fluid Mesenchymal progenitor cells (stem cell growth factors) to spontaneously differentiate into chondrocytes suggests that cell-to-cell aggregation and/or communication may be impaired in osteoarthritis and somehow dampen the normal mechanism of chondrocyte replenishment from the synovium or synovial fluid. Should the cells of the synovium or synovial fluid be a reservoir of stem cells for normal articular cartilage maintenance and repair, these endogenous sources of chondro-biased cells would be a fundamental and new strategy for treating osteoarthritis and cartilage injury if this loss of aggregation & differentiation phenotype can be overcome.”(3)

  • In common terms, the “reservoir of stem cells for normal articular cartilage maintenance and repair,” already in the knee, are not fixing the knee because of a confused communication. The joint environment has changed from healing to degenerative. The paper suggests getting these stem cells communicating and healing would create a fundamental new strategy in healing.

This research was supported in a study from December 2017 In Nature reviews. The paper suggested that recognizing that joint-resident stem cells are comparatively abundant in the joint and occupy multiple niches (from the center of the joint to the out edges) will enable the optimization of single-stage therapeutic interventions for osteoarthritis.(4) The idea is to get these native stem cells to repair.

There are a lot of stem cells in a knee waiting to repair. The problem is they are confused and not getting the correct instructions. Stem cell therapy can fix the communication problem and begin the repair process anew

Now we know that there are many stem cells in the knee, when there is damage to the knee, there are even more stem cells. If we can figure out how to get these stem cells turned on to the healing mode, the knee could heal itself of early stage osteoarthritis. So the problem is not the number of stem cells, there is a lot of them already in the knee, BUT, communication. Introduction of new stem cells with “fresh communication,” from the sideline can change that.

This failure of native stem cells to communicate the right healing instructions in a damaged knee was also seen in other research. In 2016, another heavily cited paper, this time from Tehran University for Medical Sciences, noted that despite their larger numbers, the native stem cells act chaotically and are unable to regroup themselves into a healing mechanism and repair the bone, cartilage and other tissue. Introducing bone marrow stem cells into this environment gets the native stem cells in line and redirects them to perform healing functions. The joint environment is changed from chaotic to healing because of communication.(5) It should be pointed out that 62 medical studies cited the research in this paper’s findings.

A recent paper from a research team in Australia confirms how this change of joint environment works. It starts with cell signalling a new communication network is built.

  • When introduced into a diseased joint, stem cells display plasticity and multipotency (the ability to change/morph into other cell types, multiply. They also signal the native stem cells and other growth factors to regroup and begin repairing damaged joints.)
  • Mesenchymal stem cells express various growth factors – an array of bioactive molecules that stimulate local tissue repair – These growth factors, and the direct cell to cell contact between MSCs and chondrocytes (the present remaining cartilage cells in the joint), have been observed to influence chondrogenic differentiation and cartilage matrix formation – in simple terms – stem cells regenerated cartilage.(6)

University of Iowa research published in the Journal of orthopaedic research

“Serious meniscus injuries seldom heal and increase the risk for knee osteoarthritis; thus, there is a need to develop new reparative therapies. In that regard, stimulating tissue regeneration by autologous (from you, not donated)  stem/progenitor cells has emerged as a promising new strategy.

(The research team) showed previously that migratory chondrogenic progenitor cells (mobile cartilage growth factors) were recruited to injured cartilage, where they showed a capability in situ (on the spot) tissue repair. Here, we tested the hypothesis that the meniscus contains a similar population of regenerative cells.

Explant studies revealed that migrating cells were mainly confined to the red zone (where the blood is and its growth factors) in normal menisci: However, these cells were capable of repopulating defects made in the white zone (the “desert area” where no blood flows. Migrating cell numbers increased dramatically in damaged meniscus. Relative to non-migrating meniscus cells, migrating cells were more clonogenic, overexpressed progenitor cell markers, and included a larger side population. (They were ready to heal) Gene expression profiling showed that the migrating population was more similar to chondrogenic progenitor cells (mobile cartilage growth factors) than other meniscus cells. Finally, migrating cells equaled chondrogenic progenitor cells  in chondrogenic potential, indicating a capacity for repair of the cartilaginous white zone of the meniscus. These findings demonstrate that, much as in articular cartilage, injuries to the meniscus mobilize an intrinsic progenitor cell population with strong reparative potential.”(7)

The intrinsic progenitor cell population with strong repair potential are in your knee waiting to be mobilized.

So what are we to make of this research?
There are a lot of stem cells in a knee waiting to repair. The problem is they are confused and not getting the correct instructions. Stem cell therapy can fix the communication problem and begin the repair process anew.


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References:

1 Kurth TB, Dell’accio F, Crouch V, Augello A, Sharpe PT, De Bari C. Functional mesenchymal stem cell niches in adult mouse knee joint synovium in vivo. Arthritis Rheum. 2011 May;63(5):1289-300. doi: 10.1002/art.30234.
2 Cai S, Ming B, Ye C, Lin S, Hu P, Tang J, Zheng F, Dong L. Similar Transition Processes in Synovial Fibroblasts from Rheumatoid Arthritis and Osteoarthritis: A Single-Cell Study. J Immunol Res. 2019 Jul 24;2019:4080735. doi: 10.1155/2019/4080735. PubMed PMID: 31428656; PubMed Central PMCID: PMC6681591.
3 Krawetz RJ, Wu YE, Martin L, Rattner JB, Matyas JR, Hart DA. Synovial Fluid Progenitors Expressing CD90+ from Normal but Not Osteoarthritic Joints Undergo Chondrogenic Differentiation without Micro-Mass Culture. Kerkis I, ed. PLoS ONE. 2012;7(8):e43616. doi:10.1371/journal.pone.0043616.
4 McGonagle D, Baboolal TG, Jones E. Native joint-resident mesenchymal stem cells for cartilage repair in osteoarthritis. Nature Reviews Rheumatology. 2017 Dec;13(12):719.
5 Davatchi F, et al. Mesenchymal stem cell therapy for knee osteoarthritis: 5 years follow-up of three patients. Int J Rheum Dis. 2016 Mar;19(3):219-25.
6. Freitag J, Bates D, Boyd R, Shah K, Barnard A, Huguenin L, Tenen A. Mesenchymal stem cell therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy – a review. BMC Musculoskelet Disord. 2016 May 26;17(1):230. doi: 10.1186/s12891-016-1085-9. Review.
7 Seol D, Zhou C, et al. Characteristics of meniscus progenitor cells migrated from injured meniscus. J Orthop Res. 2016 Nov 3. doi: 10.1002/jor.23472.

There is controversy in the medical community about umbilical cord blood stem cells. Some insist that the injectable solution contains abundant live umbilical cord blood stem cells. Some suggest that the stem cells are not alive. I have seen the flow cytometry showing live stem cells. The research shows that these stem cells release cytokines and growth factors that awaken native stem cells.  I have tried this treatment on myself for both shoulders and knees. After great success, I started using this treatment on patients. I still use PRP and bone marrow depending on the patient’s pathology and requirements. To date the results are excellent for all of these treatments. We are in the process of doing a study on cord blood stem cells (we have done others on bone marrow and PRP) to see which treatments are the most successful. We are awaiting more long term results.