CELL-Based THERAPY: Future of Regenerative MEDICINE in Treating SjÖgren'S Syndrome

Objective: Sjögren's syndrome (SjS) is an autoimmune disease in which a chronic progressive autoimmune attack against the salivary and lacrimal glands results in glandular hypofunction leading to dry mouth/dry eye disease. A major challenge in treating SjS patients involves replacing the acinar cell mass destroyed by pathogenic physiological or immunological element(s) activated in SjS patients. To address this challenge, two approaches are generally considered: expansion of existing acinar cells using growth and differentiation factors, or regeneration of new acinar tissue from stem/progenitor cells. Recently, we initiated studies aimed at isolating stem/progenitor cells capable of differentiating into functional acinar tissue when implanted into salivary glands of mice with SjS-like disease.

Methods: Minor salivary glands from SjS patients and submandibular glands explanted from C57BL/6.NOD-Aec1Aec2 mice were used to establish long-term cultures of cells capable of slow continuous growth and expansion. Human salivary cell lines were transfected to express eGFP. Recipient mice injected with these cultured cells are being followed for glandular reconstitution and function.

Results: Using RT-PCR, immunohistochemistry and Western blot analyses reveal temporal (positive) expressions of cytokeratins, keratins, aquaporin-1 and -5, vimentin, calponin, metallothionen and other cell markers, along with (negative) expression of alpha-amylase indicates the propagation of precursor cells. Whether these cells terminally differentiate to functional acinar tissue or have regulated expansion when injected into salivary glands of NOD, NOD-scid or recombinant C57BL/6.NOD-Aec1R01Aec2 mice is still in progress.

Conclusion: Although a few studies have begun to address in vitro growth of new tissue for replacement of acinar tissue in SjS patients, the present work focuses on use of stem/progenitor cells as an initial source. These early data should establish a solid foundation for transitioning this stem/progenitor cell-based approach to future treatment of SjS patients.

Supported by NIH grants DE014344 and T32DE07200