Bone marrow-derived mesenchymal stem cells migrate to healthy and damaged salivary glands following stem cell infusion

Abstract

Xerostomia is a severe side effect of radiation therapy in head and neck cancer patients. To date, no satisfactory treatment option has been established. Because mesenchymal stem cells (MSCs) have been identified as a potential treatment modality, we aimed to evaluate stem cell distribution following intravenous and intraglandular injections using a surgical model of salivary gland damage and to analyse the effects of MSC injections on the recruitment of immune cells. The submandibular gland ducts of rats were surgically ligated. Syngeneic adult MSCs were isolated, immortalised by simian virus 40 (SV40) large T antigen and characterized by flow cytometry. MSCs were injected intravenously and intraglandularly. After 1, 3 and 7 days, the organs of interest were analysed for stem cell recruitment. Inflammation was analysed by immunohistochemical staining. We were able to demonstrate that, after intravenous injection, MSCs were recruited to normal and damaged submandibular glands on days 1, 3 and 7. Unexpectedly, stem cells were recruited to ligated and non-ligated glands in a comparable manner. After intraglandular injection of MSCs into ligated glands, the presence of MSCs, leucocytes and macrophages was enhanced, compared to intravenous injection of stem cells. Our data suggest that injected MSCs were retained within the inflamed glands, could become activated and subsequently recruited leucocytes to the sites of tissue damage.

Mesenchymal stem cells – A new hope for radiotherapy-induced tissue damage?

“…Additionally, the salivary gland architecture appeared more preserved with more functional acini and improved microvessel formation in MSC-treated mice; the numbers of apoptotic cells were found reduced in comparison to untreated control animals [80]. Following salivary gland damage, systemically applied MSCs were reported to migrate to the damage sites in order to exert their effects [81]. Regarding the role of MSC differentiation in salivary gland damage, the published reports are somewhat controversial.…”

Mesenchymal Stromal Cells Protect Against Caspase 3-Mediated Apoptosis of CD19+Peripheral B Cells Through Contact-Dependent Upregulation of VEGF

“…It is now clear that transplanted MSC have the capacity to migrate to lymph nodes [45]. Thus the administration of MSC in concurrence with B cell activation may lead to enhanced expansion of B cells; which in the case of B cell driven or idiopathic disease may be detrimental to the patient.…”

Supportive angiogenic and osteogenic differentiation of mesenchymal stromal cells and endothelial cells in monolayer and co-cultures

“…Although studies have demonstrated that MSC-conditioned media are able to promote EC viability, 16 we hypothesize that the successful establishment of prevascularized networks is co-dependent on an endothelial and supporting MSC co-culture differentiation. Different types of MSCs have been characterized 17, 18, 19 ; however, it remains unclear whether MSCs can retain their unique osteogenic potential during angiogenic differentiation. To determine how MSC and EC contribute to a cellular interdependent proangiogenic differentiation, we analysed the differentiation of bone marrow-derived MSCs (BMSCs) and ECs under the influence of EC growth medium in monolayers, Transwells and co-cultures.…”