Transplantation of Olfactory Ensheathing Cells: Properties and Therapeutic Effects after Transplantation into the Lesioned Nervous System

Round 1

Reviewer 1 Report

In this interesting and detailed review entitled “ Transplantation of olfactory ensheathing cells: properties and therapeutic effects after transplantation into the lesioned nervous system”, the authors report the most recent findings regarding the use of Olfactory Ensheathing Cells (OECs) as therapeutic tool in the transplantation in the lesioned area of the CNS and PNS. It is known that OECs are a particular type of glial cells into olfactory system showing different peculiarities, therefore many researches focused on their use in cellular therapy. The manuscript is well written, the authors show deep knowledge on the topic, reporting a considerable number of references. Therefore, in my opinion, the review could be accepted in Neuroglia after minor revision, in order to inform the scientific world on the state of art regarding the OECs and their use.

Throughout the text there are numerous grammatical and typographic errors which should be revised and corrected, therefore I recommend the authors to review the text carefully.

Figure: I suggest to inverte fig.1 A with fig.1B, since in the text B is described before A.

Legend: “C” shuold be written in lowercase.

In pag.14: some references cited should be indicated with the first name of authors, for example Kocsis and Feron should be replace with Kato and Lu, respectively. The authors should  revise throughout the text.

Pag. 25: the reference 163 correspond to Morita and not to Huang.

Author Response

Response: First of all, we would like to thank the reviewer for his comments.

We have taken into account reviewer’s remarks and suggestions.

Reviewer 2 Report

This review describes olfactory ensheathing cells OECs in the primary olfactory system (POS). They discuss the different functional aspects of the Olfactory system and its kand the central nervous system. The OECs are a specialized set of glial cells that exhibit properties of Schwann cells and Astrocytes. They do not express a specific marker, but P75 is considered its pan marker. Overall, the paper describes OECs as a heterogeneous population, Schwann cell-like, secret trophic factors, and ECM proteins. OECs also regulate the inflammatory process of tissue repair and help with the regeneration of axons. This review explains the regrowth of axons in the PNS and CNS; unlike the Schwann cells, the mechanism stated could be its close association with fibroblast causing an open channel for axons to regenerate. The authors also explain and cite several different transplantation models in rats after SCI and peripheral injury. Finally, this paper also describes some other clinal trials performed in humans after transplantation of OECs in ALS model and SCI and they help with the recovery process.

Comments

• In your paragraph of heterogeneity of OECs population, you mention transcriptomics studies. Could you elaborate on what was done and the results as little bit more.
• OM-OECs/OB-OECs- microarray results- Can you mention a few genes that were differentially expressed in the two groups?
• “Then, transcriptomic study has confirmed that two sub populations of OECs, characterized by their differential expression”- which transcriptomic study, can you cite that study ?
• Figure quality needs to be improved with better resolution.
• English needs to improved some edits are below

Abstract

1. 4- Four
2. a specific populations- a specific population
3. could- cause
4. into- in
5. have- has
6. the scientists- scientist
7. their potentiall- potentoial
8. 30 -thirty
9. 30 years of reseaches- 30 years of research
10. Exert- exerted
11. And which allow to envisage- and allow to envisage

Organization of the olfactory system

1. Olfactory system- The Olfactory system
2. In particular the- particularly the
3. Which connect- that connect
4. In olfactory – in the olfactory
5. Themselvesto- themselves to
6. stem cells into the OE- rephrase
7. play also- also play
8. than- as
9. 6- six
10. Has led sometime- have sometimes led
11. Condition in- conditions is

Origin and cellular heterogeneity

1. Explain- explains
2. Into their specific- in their specific
3. At- ON
4. Pattern- patterns
5. Involved into- involved in
6. sub-populations- subpopulations
7. et at- et.al
8. heterogenous- heterogeneous
9. transcriptomic- a transcriptomic
10. sub population – subpopulations
11. to propose- proposing
12. as main- as the main
13. OECS used marker- OECs used markers
14. These investigation- these investigations
15. ENCAM- or E-NCAM ?
16. E-NCAM is expressed both in 8 vitro and in vivo- 8 needs to be removed
17. been also- also been investigated
18. \differentiate the markers express by OECs in vitro and those expressin vivo- markers expressed by / express in vivo
19. in vivo/ in vitro – italics
20. due to differencesin experimental paradigms,such asthe age- differences in/ such as the

Figure 1

1. quality needs improvement
2. d) cannot see blue rectangle, red, or green- borders need to be thickened
3. NGF, BDNF, GDNF or CNTF needs to be abbreviated

OECs properties

1. made the choice- made a choice
2. competences- competencies
3. P75 was used as pan marker- P75 has been used as a pan-marker
4. physiological condition- physiological conditions
5. In contrast into the OBs- In contrast to the OBs
6. Nazareth et al., shown that OECs- Nazareth et al., have shown that OECs
7. during the development of olfactory system- during the development of the olfactory system
8. continue throughout life- continues throughout life
9. Phagocytic properties of- The Phagocytic properties of
10. trafficking of endosome and lysosome- trafficking of endosomes and lysosomes
11. led up the scientists- led up  scientists

A brief History of the use of the OECs for repairing the nervous system

1. studies after spinal cord- studied after spinal cord
2. transection, show that transplantation- transection, shows that transplantation
3. X ray- X-ray
4. et al- et al.
5. in this study OM-OECs were obtained from Human.- in this study OM-OECs were obtained from humans.
6. obtained from pig- obtained from pigs
7. In 2004, was also published the first study regarding the effects of OECs transplantation after degenerative diseases.- repharse
8. of Parkinson disease- of Parkinson’s disease
9. study in Human- study in humans

Transplantation of OECs after spinal cord injury

1. transplantation after SCI is well documented- transplantation after SCI are well documented
2. to our point view- to our point of view
3. OEC transplantations are the less efficient- OEC transplantations are less efficient
4. results seem indicate- results seem to indicate
5. Others research teams- Other research team
6. Meta analysis- is not the same everywhere
7. and can even might to lead to aggravate- and can lead to aggravating
8. OECs after SCI exert- OECs after SCI exerts
9. olfactory fibroblasts is more efficient that purified- olfactory fibroblasts is more efficient than purified
10. This hypothesis has been- This hypothesis was
11. OECs can secreted anti-inflammatory- OECs can secret anti-inflammatory
12. X- 20 ray- is it X-ray?
13. the first reporting- the first to reports
14. SCs in irradiated- SCs in an irradiated
15. 3 weeks old rats have been- three weeks old rats were irradiated

 Transplantation of OECs after peripheral nerve injury

1. within the two fist weeks after- within the two first weeks after

OECs transplantation in other CNS injury models

In in a first time- In the first time

1. In in a first time, the studies conducted in animal models will be introduced and discussed, then in a second time clinical related studies will be presented.-repharse
2. In the second model, authors- In the second model the authors
3. enhances significantly- significantky enhances
4. Since decade,- For a decade
5. Wang et al, demonstrate- demonstrated
6. cell typesin TBI mode-cell types in TBI mode
7. confirm those describes- confirm those described
8. In fact, NSS is improved in OECs or BMSC groups but the maximum 24 efficiency is obtained by co-transplantation of these 2 cell types.-repharse
9. Two studies based on stroke model- Two studies based on the stroke model
10. transplantation reduces infract- infarct
11. reduction of mortality- a reduction of mortality
12. OECs in animal model- OECs in an animal model
13. tumor growth and increase- tumor growth and increased
14. confirmed in human-confirmed in humans
15. bilateral transplant- bilateral transplants
16. Interestingly, as describe- Interestingly, as described
17. OECs transplantation with exogenous additional- OECs transplantation with additional exogenous
18. Demonstrate- demonstrated
19. used as vector to deliver- used as a vector to deliver
20. overcome in a near future- overcome in the near future

Author Response

Response: First of all, we would like to thank the reviewer for his comments.

We have taken into account reviewer’s remarks and suggestions.