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itMesenchymal stromal cells (MSC) are progenitor multipotent non-hematopoietic cells able to auto-renewal and differentiate into mesodermal cell lineages.
MSC can be isolated from different human tissues, where they could be recognized as pericytes, and used as cellular source for tissue repair and regeneration. Although the bone marrow represents the main and approved source of MSC for clinical use, due to the invasive procedure for its collection, alternative MSC sources have interested the scientific community. In this contest, the umbilical cord blood (UCB), collected in non-invasive manner and without ethic concerns, is evaluated as alternative source than bone marrow.
Currently, MSC definition is based on three criteria defined by International Society for Cellular Therapy (ISCT): plastic adherence under standard culture conditions; expression of CD105, CD73, CD90 markers and absence of hematopoietic and endothelial markers as CD14, CD45, CD34, CD11b, HLA-DR and CD31; in-vitro differentiation potential under specific culture condition into osteocytes, chondrocytes and adipocytes. These criteria also represent the accepted standard by scientific community to characterize human MSC, despite functional and phenotypic differences exist between different tissue sources, culture conditions and extended ex-vivo expansion. Flow cytometry is currently the gold standard to study the MSC immunophenotype as part of quality evaluation for MSC product release according to GMP guidelines.
Our Laboratory is specialized in the isolation, characterization and ex-vivo expansion of mesenchymal stromal cells from perinatal tissue sources like umbilical cord (UC-MSC) and umbilical cord blood blood-derived MSC (UCB-MSC). Perinatal MSCs are different from MSC isolated from adult sources like bone marrow for their high proliferative capacity and their peculiar trophic and differentiation properties. Therefore, UCB-MSC maintain a low immunogenicity that take them feasible for allogeneic use.
The possibility to obtain MSC ready to use from this source and generated in authorized GMP facilities, allows to test the MSC immunomodulatory and regenerative properties in controlled clinical experimentation.
The Laboratory owns an optimal background with regard to the ability of isolation the MSC from sources such as adipose tissue and bone marrow. The latter is obtained through the washout of bone marrow transplant bags. Adipose tissue (liposuction) and umbilical cord represent also good sources of MSC. These tissues are digested by enzymes to allow their disaggregation and the efficiency of MSC isolation is very high.
Currently, the consolidated use of these cells belongs to acute or chronic Graft versus Host Disease (GvHD) therapy after hematopoietic stem cells transplant. GvHD is an immunological reaction due to donor’s immunocompetent cells towards recipient’s tissues. With allogeneic bone marrow transplantation, the donor's immune system is infused into the recipient together with the hematopoietic stem cells. It follows a situation of competition between immune systems: a reaction of the recipient’s immunocompetent cells towards the transplanted tissue and a reaction of the immunocompetent organ transplanted towards the recipient’s tissues. The targets of immune reaction that cause GvHD are predominantly the basal layer of epidermis and gastrointestinal mucosa; biliary ductal epithelium; exocrine glandular epithelium and hematopoietic marrow stem cells.
There is an acute and a chronic form of GvHD in relation to the moment of manifestation and its clinical characteristics. The acute form of the disease is observed within the first 100 days from the date of transplantation. It is manifested by death of skin, liver and gastrointestinal epithelial cells with related symptoms such as diarrhea, hemorrhage, jaundice and rash. If cell death is extensive, this GvHD can be deadly for the transplanted patient.
The chronic form instead begins after this period. It is characterized by fibrosis and atrophy of the same organs affected also by acute GvHD, without evident acute cell death. It can also involve the lungs causing obliteration of the airways. It is hypothesized that chronic GvHD is the body's fibrotic response that attempts to contain the damage caused by acute GvHD, but may also represent a response to ischemia caused by vascular damage. The distinctions between the two types also include other factors, not limited to a simple timing of the event.