Regeneration of human bones in hip Osteonecrosis and human cartilage in knee Osteoarthritis with autologous Adipose-tissue-derived stem cells：a case series（5）
Discussion
This series of clinical case reports provides clear MRI evidence of apparent bone regeneration in osteonecrosis of femoral heads and meniscus cartilage regeneration in osteoarthritis of human knees. Based on the MRI features, it is probable that the new tissue formation is bone matrix in the case of osteonecrosis and meniscus cartilage in osteoarthritis. However, without biopsy, the true nature of the newly-formed tissue is unclear. While bone and cartilage regeneration using ADSCs has been shown in animal models, these case reports represent the first successful regeneration of bones and cartilage in human patients.
In addition to the MRI evidence, the patients' symptoms and signs also improved. It is worthwhile to note that the patients' symptoms improved gradually over three months. Thus, it can be speculated that, in patients with osteonecrosis, newly-formed bone has concomitant neovascularization. Osteonecrosis, or avascular necrosis, occurs due to compromise in blood circulation. Without concurrent neovascularization, the consolidation or regeneration of bones cannot be sustained.
Another issue with these clinical results is that patients with osteoarthritis did not report 100% symptom improvements. This may be due to the fact that osteoarthritis is a disease of the whole knee, not just the cartilage.
With regard to the mechanism of tissue regeneration, there are a few plausible possibilities. The mechanism of regeneration could be through direct differentiation of stem cells that were introduced through the injection. However, there is a possibility that the ADSCs exert tropic effects on the existing tissues as well. Numerous studies have reported that MSCs, in addition to tissue repair and regenerative effects, have immunomodulatory and paracrine effects [14].
Furthermore, PRP could have contributed to the regeneration of bones and blood vessels. PRP contains multiple growth factors including TGFβ, IGF, FGF, and PDGF. A literature review of the data on the uses of PRP showed that it has a positive effect on the stimulation of bones and blood vessels and chondrocytes. Here, it was used as a growth factor and as a differentiating agent for the MSCs.
Further, Dexamethasone injection, used as a differentiating agent for Cartilage, may also have had positive effects in patients with osteoarthritis. The levels injected (100 ng/mL) were negligible compared to the doses being used in clinical settings. Such low doses in the nanogram range have been shown to increase extracellular matrix production by chondrocytes, and are commonly used in vitro to differentiate MSC from cartilage [15].
This is the first series of case reports showing possible successful bone and cartilage regeneration in humans by using a combination of ADSCs, hyaluronic acid, PRP and CaCl2. Currently, no non-surgical therapy is available for the treatment of osteonecrosis and osteoarthritis. Thus, stem cell therapy may significantly improve current treatment strategies for the treatment of knee osteoarthritis and osteonecrosis of the femoral head. However, further studies need to be initiated to find out the true detailed nature of the apparently regenerated bones and cartilage and to determine the true mechanism of tissue regeneration.
Conclusions
After three months of treatment, all the patients reported on above were able to straighten their hips and extend their knees further, affecting MRI postures. Therefore, obtaining the post-treatment MRI data at the exactly same location as pre-treatment MRI of the hips and knees was difficult.
Although there were difficulties in repeatedly obtaining the exact location of the hips and knees, the pre-procedure and post-procedure MRI analyses clearly demonstrate filled bone defects in osteonecrosis and increased meniscus cartilage volume in osteoarthritis, indicating regeneration attributable to the ADSC treatment. Additionally, the measured physical therapy outcomes, subjective pain, and functional status, all improved
Consent
Written informed consent was obtained from all patients for publication of this case report and any accompanying images. Copies of the written consents are available for review by the Editor-in-Chief of this journal.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
JP was in charge of patient treatment and follow-up, was responsible for manuscript drafting and revision, and read and approved the final manuscript.
Acknowledgements
JP acknowledges the support from the staff of Miplant Stems Clinic.
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