*Molecular Challenges and Advances in Clinical Islet Transplantation DOI: http://dx.doi.org/10.5772/intechopen.108571*

Cell-free circulating DNA (cfDNA), is now recognized as a potential biomarker for a variety of diseases. In humans, the insulin promoter is predominantly unmethylated in islet *β*-cells and methylated in all other tissues. cfDNA-based estimation of beta cell death 24 hours after islet allotransplantation correlates with clinical outcome and could predict early engraftment [14].

To understand on the beta cell function and beta cell mass, high-quality pancreatic islets are essential as they correlate with better post transplantation endocrine function. Islet quality and yield get affected by stress during the isolation process. During isolation, islet-enriched microRNAs (miRNAs) -375 are released and they serve helpful in assessing the extent of islet damage by correlating with post transplantation endocrine function. Assessment of the absolute concentration of miR-375 C-peptide at various islet isolation steps, including digestion, dilution, recombination, purification, and bagging is possible. Measurement of the absolute quantity of miRNA-375 during islet isolation is a useful tool to assess islet damage. The quantity of released miRNA is indicative of post transplantation endocrine function in transplant patients [15–17].

Better engraftment and functioning of islets needs to be proved by the production of Insulin for the alleviating problematic hypoglycemia before and after islet transplant. This can be done by constantly monitoring the insulin level by various methods. CD30 levels are a predictor marker for acute rejection before and after the islet transplant. Elevated CD30 levels may reflect an immune state detrimental for islet allograft survival. In islet allograft recipients, post-transplant reduction in sCD30 levels can serve as a biomarker to monitor graft function. Furthermore, an insight on how various immunosuppression protocols impact the timing and extent of changes in post-transplant sCD30 levels may facilitate patient-specific tailoring of immunosuppression [18, 19].

HMGB1 is a mediator of immune system during islet transplant. HMGB1 is one of the best-characterized DAMP molecules associated with islet. HMGB1 seemed to be released by damaged islets before and after transplant. HMGB1 will be one of the useful bio signatures detecting islet damage in clinical situation. It is the need of the hour for more research and development of kits in these area to bring the islet product release criteria that screen preparations before and after clinical allogeneic islet cell transplantation that are currently unavailable to predict post-transplant success from failure. More sensitive and reliable islet viability, potency kits and assays that characterize cell composition and molecular profiles will be useful in further defining the islet product and may provide useful information on islet immunogenicity and pro-inflammatory potential to evaluate islet functionality in the clinical setting [20, 21]. The following figure, **Figure 3** is a pictorial representation of 'development of molecular Bio Signatures- pre and post- islet cell transplantation.

A transplantation outcome that curtails infection and rejection is desirable; still, the present day immunosuppression strategies using prophylactic antimicrobial medications do not guarantee this! Human leukocyte antigen matching is an important aspect of graft survival. However, other factors like extent of immunosuppression, infections and management of comorbidities is also crucial. Considering transplant patient's predisposing genetic modifiers for risk stratification and as a basis for applying precision pharmacotherapy may improve transplant outcomes [22].

The most important genes deciding the fate of a transplanted cell, tissue, or organ belong to what is termed the MHC (the major histocompatibility complex). The MHC antigens' primary function is to aid in distinguishing self from no-self through peptide presentation to the immune system. The MHC antigens are also termed as
