Wednesday, May 24, 2017

Injection of Stem Cells Around the Lacrimal Gland: Proof That Mesenchymal Stem Cells Help with Dry Eye and Other Disorders.

The injection of Stem Cells Around the Lacrimal Gland has been performed in dogs with good success as noted below. This has also been tried in humans with Sjögren's syndrome with good results but it has not been published yet. I am hoping to start a funded protocol to study stem cell injections into the Meibomian Glands and around the Lacrimal Gland in our severe dry eye patients. We would use Autologous Stem Cells: a patient's own stem cells.

This study below shows the benefit of Allogeneic (not your own stem cells) Mesenchymal Stem cells injected near the dog's lacrimal gland. These dogs had Keratoconjunctivitis sicca (KCS), also known as “dry eye syndrome, which is usually due to lacrimal gland inflammation. This treatment could theoretically work on humans who have Sjögren's syndrome is primarily a lacrimal gland inflammation. However, Sjögren's syndrome also destroys meibomian glands and I believe anyone who has stage 3 (advanced; staging depends on which staging you use) MG loss, should have an SJO test: not just anti-Ro, anti-La. I have picked up early Sjögren's  in many patients because of a positive SJO test for early Sjögren's syndrome antibodies before the anti-Ro and anti-La became positive. 


After they did liposuction on the dogs and isolated the stem cells with collagenase, they inserted a syringe through the conjunctival fornix of the superior eyelid, into the dorsolateral region of the ocular bulb, below the orbital ligament close to the lacrimal gland. The remaining 0.2 ml of cell suspension was injected into the third eyelid Lacrimal gland, which was accessed through the bulbar face of the third eyelid. 
The only treatment allowed for animals in this study, besides the MSC transplantation itself, was the use of artificial tears (sodium hyaluronate 0.2%) in the cases of severe KCS, which is used in order to maintain animal comfort. This type of lubricant has topical and immediate action and does not interfere with tear production. The administration of the artificial tear occurred three times per day over the first 30 days after MSC transplantation.

An improvement was seen in about 28 days with 1 injection. 

Here is before and after photos of the corneas of the dogs: the column on the left A-D is before stem cell injections. The column on the very right is after injection A"-D":

For our protocol, we would be using  Autologous (your own stem cells) and injecting them into the canal of the meibomian gland.

Here is more information below.


. 2016 Dec 3; 8(3): 63–77.
Published online 2016 Oct 18. doi:  10.3727/215517916X693366

PMCID: PMC5165646

Allogeneic Mesenchymal Stem Cell Transplantation in Dogs With Keratoconjunctivitis Sicca



Keratoconjunctivitis sicca (KCS), also known as “dry eye syndrome,” is a common ocular disease in dogs resulting from lacrimal gland (LG) inflammation and decreased tear production. KCS can occur either as a quantitative deficiency in the aqueous component of tears or as a qualitative deficiency in the lipid or mucin layers of the tear film, causing tear film instability, with potential damage to the ocular surface. This damage is characterized by the presence of mucoid ocular discharge, conjunctival hyperemia, blepharospasm, recurrent corneal ulceration, corneal vascularization, fibrosis, and, eventually, corneal pigmentation. In severe cases, dense corneal opacification (clouding) or corneal perforation secondary to deep ulceration can lead to blindness or even loss of the eye. The diagnosis of quantitative KCS is based on typical ocular surface changes, as well as on dysfunction in tear production, which is evaluated by biomicroscopy of the anterior segment and by the Schirmer tear test (STT), respectively. The STT determines whether the eye produces enough tears to keep it moist and ranges from normal (15–25 mm/min), mild (9–14 mm/min), moderate (>4 to 8 mm/min), to severe (≤4 mm/min).
Any condition that impairs the ability to produce adequate amounts of tear film can result in KCS. Local immune-mediated disease is the most widely accepted cause of KCS based on histopathology of tear-producing glands and on the clinical response to immunomodulators. However, other systemic diseases may also be associated with KCS, such as infection with canine distemper virus, hypothyroidism, diabetes mellitus, and Cushing’s disease. In addition, systemic administration of pharmaceutical agents for long periods and at high doses has also been reported to cause dry eye. The most common treatment for KCS is the prescription of immunosuppressive drugs, such as cyclosporine and tacrolimus, which may need to be used indefinitely. Furthermore, some authors believe a small number of dogs are resistant to the action of cyclosporine. It is important to explain to the owner that the dog with KCS needs constant care, such as removal of secretions from around the eyes many times a day to minimize irritation of the eyelids, conjunctiva, and cornea. Thus, efforts are being made to develop alternative therapies to inhibit the immune response and inflammatory processes in order to reduce the suffering of animals with KCS and the need for their constant care.
It is known that mesenchymal stem cells (MSCs) are powerful regulators of the immune response and that they have been shown to be effective in treating various immune disorders in human and animal models. Previous studies have already demonstrated safety aspects of MSC transplantation into the LG and tear production improvement after MSC transplantation in dogs with KCS. However, it remains unclear whether MSC transplantation is efficient and leads to a good prognosis—tear production levels reverting to normal—in cases of severe KCS, especially in the long term. We thereby carried out the present study to evaluate the effects of MSC transplantation into LGs on tear production and clinical signs in dogs with mild–moderate versus severe KCS.
Veterinary patients, such as dogs, are increasingly recognized as critical translational models of human diseases because the etiopathogenesis of canine diseases is similar to that of humans, particlularly regarding Sjögren’s syndrome. Sjögren’s syndrome is a systemic autoimmune disease diagnosed by its two most common symptoms—dry eyes and dry mouth. For this reason, canine KCS studies may aid in the development of therapeutic interventions that can benefit humans. Over the last few years, there has been an increase in the demand for sophisticated therapies, such as the use of stem cells, in animal companion care, which has led to a surge in stem cell studies using dogs. These studies should provide a unique opportunity for assessing both efficacy and safety of human adult stem cell therapies that can be translated to human medicine.

References:
1. Beyer Nardi N, da Silva Meirelles L. Mesenchymal stem cells: Isolation, in vitro expansion and characterizationHandb Exp Pharmacol. 2006(174):249–82. [PubMed]
2. Stern ME, Schaumburg CS, Pflugfelder SC. Dry eye as a mucosal autoimmune diseaseInt Rev Immunol. 2013;32(1):19–41. [PMC free article] [PubMed]
3. Gonzalez MA, Gonzalez-Rey E, Rico L, Buscher D, Delgado M. Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responsesGastroenterology2009;136(3):978–89. [PubMed]
4. Rafei M, Campeau PM, Aguilar-Mahecha A, Buchanan M, Williams P, Birman E, Yuan S, Young YK, Boivin MN, Forner K, Basik M, Galipeau J. Mesenchymal stromal cells ameliorate experimental autoimmune encephalomyelitis by inhibiting CD4 Th17 T cells in a CC chemokine ligand 2-dependent mannerJ Immunol. 2009;182(10):5994–6002. [PubMed]
5. Zappia E, Casazza S, Pedemonte E, Benvenuto F, Bonanni I, Gerdoni E, Giunti D, Ceravolo A, Cazzanti F, Frassoni F, Mancardi G, Uccelli A. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergyBlood 2005;106(5):1755–61. [PubMed]
6. Hoogduijn MJ, Popp F, Verbeek R, Masoodi M, Nicolaou A, Baan C, Dahlke MH. The immunomodulatory properties of mesenchymal stem cells and their use for immunotherapyInt Immunopharmacol. 2010;10(12):1496–500. [PubMed]
7. Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R, Moseley A, Hoffman R. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivoExp Hematol. 2002;30(1):42–8. [PubMed]
8. Ryan JM, Barry FP, Murphy JM, Mahon BP. Mesenchymal stem cells avoid allogeneic rejectionJ Inflamm. 2005;2:8. [PMC free article] [PubMed]
9. Parekkadan B, Milwid JM. Mesenchymal stem cells as therapeuticsAnnu Rev Biomed Eng.2010;12:87–117. [PMC free article] [PubMed]
10. Villatoro AJ, Fernandez V, Claros S, Rico-Llanos GA, Becerra J, Andrades JA. Use of adipose-derived mesenchymal stem cells in keratoconjunctivitis sicca in a canine modelBiomed Res Int. 2015;2015:527926. [PMC free article] [PubMed]
11. Park SA, Reilly CM, Wood JA, Chung DJ, Carrade DD, Deremer SL, Seraphin RL, Clark KC, Zwingenberger AL, Borjesson DL, Hayashi K, Russell P, Murphy CJ. Safety and immunomodulatory effects of allogeneic canine adipose-derived mesenchymal stromal cells transplanted into the region of the lacrimal gland, the gland of the third eyelid and the knee jointCytotherapy 2013;15(12):1498–510. [PubMed]
12. Wood JA, Chung DJ, Park SA, Zwingenberger AL, Reilly CM, Ly I, Walker NJ, Vernau W, Hayashi K, Wisner ER, Cannon MS, Kass PH, Cherry SR, Borjesson DL, Russell P, Murphy CJ. Periocular and intra-articular injection of canine adipose-derived mesenchymal stem cells: An in vivo imaging and migration studyJ Ocul Pharmacol Ther. 2012;28(3):307–17. [PMC free article] [PubMed]

1 comment:

  1. Yes, you are right. Nowadays Stem Cell Therapy has enough potential to treat almost 72 diseases.

    ReplyDelete

Note: Only a member of this blog may post a comment.