Imagine this clinical scenario: you are presented with a client’s seven-year-old female domestic shorthair cat that you diagnosed with feline chronic gingivostomatitis (FCGS) six months previously. At the time, you performed a full-mouth tooth extraction and administered supportive treatment, but the client has returned as the patient is still in pain and has not gained weight. The owner declines the use of oral or injected corticosteroids or oral cyclosporin due to concerns over side effects. You therefore need to consider other treatment options that can improve the cat’s quality of life. A colleague has read about intravenous mesenchymal stem cell (MSC) therapy and suggests it as a potential solution.
The evidence
Five interventional studies were found that explored the efficacy and safety of MSCs when used to treat cats with FCGS. Four of the studies (Arzi et al., 2016, 2017, 2020, 2021) investigated the use of autologous or allogenic adipose-derived MSCs, while the fifth study (Febre et al., 2022) investigated the use of placenta-derived MSCs. Four of the papers (Arzi et al., 2016, 2017, 2020; Febre et al., 2022) studied the use of MSCs after partial or total tooth extraction, whereas Arzi et al. (2021) studied the use of MSCs when no tooth extraction had taken place.
All four studies by Arzi et al. (2016, 2017, 2020, 2021) were uncontrolled clinical trials with sample sizes of 9, 7, 18 and 5, respectively. All cats were client-owned and had shown signs of FCGS. These four papers followed a similar pattern of intervention: they all ensured that subjects were not on corticosteroid or other immunosuppressive therapy during the trial and for the two weeks before the study started. Each patient then received two intravenous transfusions of stem cells, one month apart. All cats were hospitalised for monitoring post-treatment and then evaluated at regular intervals after discharge.
Febre et al. (2022) was an uncontrolled clinical trial that studied eight client-owned cats that had presented to veterinary clinics with FCGS. Corticosteroids were discontinued two weeks before the study commenced and were not given to patients while the study was ongoing. All patients received a single intravenous transfusion of mesenchymal stem cells, with follow-up evaluations carried out at intervals following discharge.
Limitations of the evidence
All of the studies had small sample sizes and failed to provide [sample size] justifications, which limits the generalisability of results and doesn’t consider the potential impacts of confounding factors
All of the studies reviewed had weaknesses that reduced the overall strength of the findings. Issues that were common across all five papers included the lack of independent control groups, blinding and randomisation, all of which make the findings less generalisable and robust, as well as introducing the possibility of bias. Additionally, all of the studies had small sample sizes and failed to provide sample size justifications, which limits the generalisability of results and doesn’t consider the potential impacts of confounding factors such as age, sex, weight, breed and disease severity. Finally, four of the five papers reviewed had the same lead author (Arzi et al., 2016, 2017, 2020, 2021) and, as such, had many of the same limitations.
Summary of findings
The studies provide a moderate level of evidence in support of the use of intravenous mesenchymal stem cells as an effective treatment in cats with FCGS following a sub-total or total dental extraction. However, these findings must be considered with the limitations above taken into account.
Four of the papers (Arzi et al., 2016, 2017, 2020; Febre et al., 2022) provide support for the efficacy of MSCs when used to improve clinical signs in cats with FCGS that have undergone tooth extraction. Arzi et al. (2016) found that of the seven cats that completed the study, three went into clinical remission, two experienced substantial clinical improvement and two had minimal or no clinical response. Arzi et al. (2017) found that four out of seven cats responded positively to the treatment; two saw substantial clinical improvement, and two went into complete remission.
The studies provide a moderate level of evidence in support of the use of intravenous mesenchymal stem cells as an effective treatment in cats with FCGS following a sub-total or total dental extraction
Arzi et al. (2020) found that 13 out of 18 cats responded positively to the treatment, five of which completely recovered, and eight of which had a marked resolution of clinical signs. The remaining five cats had no response to the treatment. Febre et al. (2022) found that all eight cats studied showed some level of clinical improvement when examined six months after treatment. Four cats showed “good” improvement, two cats showed “moderate” improvement and two cats showed “mild” improvement when scored against the stomatitis disease activity index (SDAI).
However, the study by Arzi et al. (2021), which examined cats that had not undergone any tooth extractions, found that use of MSCs did not lead to substantial improvement. In this paper, three of the five cats studied did not display any clinical improvement, while two out of five cats exhibited “mild” clinical improvement.
In terms of patient safety, the findings from all papers indicated that MSC therapy is well tolerated by cats with FCGS. One cat studied by Arzi et al. (2020) experienced skin necrosis at the site of injection, requiring a skin graft, but this was the only major side effect noted across all five studies. Most side effects were mild to moderate in severity, including transfusion reactions, increased respiratory rate, vomiting and diarrhoea, all of which resolved spontaneously or therapeutically with no further complications (Arzi et al. 2016, 2020).
Conclusion
The evidence available provides moderate evidence in support of using intravenous MSCs to treat cats with FCGS when it is carried out following total or sub-total dental extraction. However, the limitations of the evidence must be considered, which include small sample sizes, lack of independent control groups and lack of blinding. There is a need for further randomised, double-blinded, controlled trials with larger sample sizes to enhance the strength of evidence and eliminate any potential biases.
| The full Knowledge Summary can be read in RCVS Knowledge’s open access journal Veterinary Evidence. |
Disclaimer
The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise; patient’s circumstances and owner’s values; country, location or clinic where you work; the individual case in front of you; and the availability of therapies and resources.
