MSC Transplantation Improves Lacrimal Gland Regeneration after Surgically Induced Dry Eye Disease in Mice

Abstract

Dry eye disease (DED) is a multifactorial disease characterized by a disrupted tear film homeostasis and inflammation leading to visual impairments and pain in patients. Aqueous-deficient dry eye (ADDE) causes the most severe progressions and depends mainly on the loss of functional lacrimal gland (LG) tissue. Despite a high prevalence, therapies remain palliative. Therefore, it is of great interest to develop new approaches to curatively treat ADDE. Mesenchymal stem/stromal cells (MSC) have been shown to induce tissue regeneration and cease inflammation. Moreover, an increasing amount of MSC was found in the regenerating LG of mice. Therefore, this study investigated the therapeutic effect of MSC transplantation on damaged LGs using duct ligation induced ADDE in mice. Due to the transplantation of sex-mismatched and eGFP-expressing MSC, MSC could be identified and detected until day 21. MSC transplantation significantly improved LG regeneration, as the amount of vital acinar structures was significantly increased above the intrinsic regeneration capacity of control. Additionally, MSC transplantation modulated the immune reaction as macrophage infiltration was delayed and TNFα expression decreased, accompanied by an increased IL-6 expression. Thus, the application of MSC appears to be a promising therapeutic approach to induce LG regeneration in patients suffering from severe DED/ADDE.

Lacrimal Gland Microenvironment Changes After Obstruction of Lacrimal Gland Ducts

“… 16 It has been found that injection of mesenchymal stem cells or mesenchymal stem cell secretomes can help lacrimal gland regeneration. 41 , 42 In the current study, the number of mesenchymal cells increased in response to two weeks of stimulation with lacrimal duct obstruction. However, longer-term duct obstruction will lead to a decrease in the number of vimentin-positive cells, and it is speculated that the imbalance of lacrimal gland homeostasis at this time leads to cell differentiation or death.…”

Dental follicle mesenchymal stem cells ameliorated glandular dysfunction in Sjögren’s syndrome murine model

“…The injections of DFMSCs were done with three injection ways as described before [ 10 – 12 ] with some modifications as follows; I) İntraperitoneal injection: 1x10 6 cells suspended in 0.5 mL of PBS was injected intraperitoneally with a 28-gauge needle [ 10 ]. II) Submandibular gland injection: 1x10 6 cells suspended in 0.1 mL PBS, and injected in the submandibular gland below the throat line of the mouse with a 29-gauge needle [ 11 ].…”

“…II) Submandibular gland injection: 1x10 6 cells suspended in 0.1 mL PBS, and injected in the submandibular gland below the throat line of the mouse with a 29-gauge needle [ 11 ]. III) Lacrimal gland injection: 1x10 6 cells suspended in 20 μL PBS was injected in the extra orbital lacrimal gland through the front of the ear line with a 27-gauge needle [ 12 ]. All injections were done on day 126.…”

Innate Immunity and Biological Therapies for the Treatment of Sjögren’s Syndrome

“…injection, showed that, despite a positive temporary effect of this treatment on the lacrimal gland function, BMSC did not engraft into the epithelial component of the gland [264]. Several other studies also reported the therapeutic benefits of MSCs, even though engraftment of these cells into the epithelial compartment of the lacrimal gland was not detected [265,266].…”