Treatment of Canine Type 1 Diabetes Mellitus: The Long Road from Twice Daily Insulin Injection towards Long-Lasting Cell-Based Therapy
, Annemarie W. Y. Voorbij 2, Elisa C. Pereira 1, Leonor M. M. Alves e Almeida 3, Geanne R. Moraes 3, Joana T. De Oliveira 3, Boyd H. T. Gouw 2, Sabrina A. M. Legatti 3, Hans S. Kooistra 2, Bart Spee 2, Andre M. C. Meneses 3,* and Louis C. Penning 2Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsIn my opinion, this review article should be widely read by many dog's owners. Dogs hardly inform their condition to their owners, and the owners hardly notice symptoms of diabetes in early stage. Daily Insulin injections might be burdens for both owners and dogs. It is extremely saddening that many owners had to decide euthanization due to the advance of diabetes. I strongly agree with establish radical therapy for canine diabetes.
This review is well designed because they focus of physiology of canine pancreatic islets, current therapies and possibility of transplantation and regenerative therapies, which is and will be applied to diabetes in human, for curing canine diabetes.
I have several comments.
1. 5. Organogenesis and physiology of the endocrine pancreas: As the authors mentioned, there are similarity between canine and human islets including that islets are consisted of 5 endocrine cellular components. On the other hand, in my opinion, the percentage of alfa cells might be higher in dog. Please include the difference of pancreas and islet between dog and human in this chapter.
2. 5. Organogenesis and physiology of the endocrine pancreas: the authors show the possibility of pancreatic organoids derived from various multipotent stem cells as donors of beta cells. However, I am wondering why the organoids should be used. I think there are no problems in direct differentiation from stem cells to beta cells. The characteristics of organoids are unclear, because pancreas is consisted of three different cell types, acinar, ductal and islet cells. In my experience, pancreatic organoids show the characteristics as pancreatic duct. Please focus on the organoids in more detail.
3. 6.3. Pancreatic or islet allotransplantations. In my opinion, pancreatic and islet allotransplantation are nonsense therapies, because one or more donor dogs have to be sacrificed for rescuing a diabetic dog. If the authors consider that these therapies are promising, please indicate the candidates (cadaver and brain dead donors?). Instead, I consider xenotransplantation using larger farm animals are recommended. Please discuss.
4. 8. Discussion and future perspective. Please show the opinion for promising therapy for canine diabetes. I consider insulin infusing therapy with monitoring continuous blood glucose and regenerative therapy using iPS (obtaining autologous stem cells derived from bone marrow and adipose tissue is stress for the dogs. Obtaining skin tissue might be acceptable) will be future promising therapies for dogs in diabetes. Furthermore, screening for detecting early diabetes will be rescue many dogs. Please discuss the importance.
Author Response
We accepted and did all modification as required.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Comments and Suggestions for AuthorsComments
Line 12: The sentence “In dogs, diabetes mellitus type 1 (T1DM) is most common” is not complete
Line 66: Please change “…are regarded life-threatening conditions” to “…. are regarded as life-threatening conditions”
Lines 86-87: The sentence “This prompted pet the food industry to formulate specific commercial diabetic dog food.” is not clear. Please rephrase
Line 120: Please label the Islet of Langerhans in Fig. 1
Line 128: Please define “PP” before use
The authors should include a table where the advantages and disadvantages of each therapeutic modalities are listed
Author Response
we accepted all the suggestions.
Author Response File: Author Response.pdf
