In addition to the cryopreservation of cord blood stem cells, Bioscience Institute operates in the promotion and support of projects in clinical and preclinical research. The main objective of this research is the discovery of new, safe and effective therapeutic applications for cell therapy products that the cell-factory is able to offer. For this reason Bioscience Institute collaborates with research groups of prestigious Italian universities and doctors of international repute. PRE-CLINICAL RESEARCH PROJECTS

Determination of the effects of increasing platelet gel concentrations on the proliferation and differentiation of different cell populations.

Platelet gel is a blood product with non trasfusional use containing several Platelet Derived Growth Factors that spread from the gel and support tissue repair. The therapeutic potential of platelet gel has been widely proved both in vitro and in vivo but there is a lack of conformity regarding the data reported in literature. This is probably due to the fact that platelet gel is used as a supplement to normal culture media, without considering the initial concentration of platelets/ul. We are therefore evaluating what are the optimal platelet gel concentrations able to induce the proliferation and/or differentiation of different cell populations: fibroblasts, keratinocytes and Adipose-Derived Stem Cells.
ONGOING – University of Bologna

Optimization of Adipose Derived Stem Cells isolation techniques.

It has been shown how a good isolation rate and expansion ability of Adipose Derived Stem Cells in culture depends both on the technique used to collect the fat and the technique used to isolate the stem cells. In order to standardize and improve the quality and the ADSC isolation rate, we are evaluating different protocols that foresee the mechanical homogenization or the enzymatic digestion as first step to isolate the cells from the fat.
ONGOING

Evaluation of adult Adipose Derived Stem Cells multipotency and their ability to differentiate into cardiomyocytes or pericytes.

ADSC can be widely used for different clinical applications in regenerative medicine as they are easily isolated from the fat, they can be collected from the patient himself, they have a good proliferative ability in vitro, they have low immunogenicity, they are able to integrate into the receiving tissue and interact with the surrounding tissues through paracrine mechanisms. Different studies have also shown that ADSC are able to differentiate into cell populations of the mesenchymal line (adipocytes, osteocytes, chondrocytes, smooth and skeletal muscle cells, heart muscle cells) but also into vascular endothelial cells, neurons, hepatocytes, pancreatic cells and hematopoietic cells. Thanks to their pluripotency, ADSC are frequently used to repair damaged tissues. The purpose of this project is to to evaluate the effects of the treatment with ADSC with physical stimulus combined to a cocktail of synthetic molecules able to increase the efficiency and reproducibility of their differentiation into cardiomyocytes or pericytes.
ONGOING – University of Milan Bicocca

Analysis of the mechanisms responsible for vitiligo.

Vitiligo is a chronic condition that causes a loss of skin pigmentation, caused by an alteration into the amount and functionality of the melanocytes. The causes of this disorders are still unclear, there are different hypothesis: genetic, autoimmune, biochemical, and neuronal. It’s been shown how melanocytes took from non affected areas of the patients are more sensitive to oxidative stress, which is thus a possible marker for this disease. In order to prove this hypothesis, in vitro experiments on melanocytes isolated from healthy and vitiligo patients are being performed.
ONGOING – Istituto Dermatologico San Gallicano Rome

Evaluation of the secretory activity of Adipose Derived Stem Cells.

Adipose tissue actively participates to the endocrine secretion through cytokines and growth factors secretion. Adipose Derived Stem Cells too are able to release growth factors and cytokines with angiogenetic and anti apoptotic properties. The purpose of this project is to analyze the molecules contained within the secretome released into the culture medium durig ADSC proliferation. ADSC are often used inside biodegradable scaffolds. The analysis of the secretome is also performed after the cells are seeded into a regular meshed polylactic scaffold to highlight possible variations and validate the scaffold system.
ONGOING – University of Bologna

Development of new scaffolds for tissue engineering applications.

Any material used as a scaffold,has to be biocompatible, biodegradable, elastic and resistant.Silk fibroin has been used to realize bioresorbable skin substitutes made by a layer of fibroin and adult stem cells isolated from adipose tissue. Those layers showed good results for the obtention of engineered skin (Chlapanidas et al., AICC, 2010).

Use of adult Adipose Derived Stem Cells for the inversion and or blocking of miniaturization process.

The follicle can be considered as a mini organ characterized by growth cycles and loss of hair, that regrows thanks to the synergic activity of its pool of stem cells. Miniaturization is a degenerative process that progressively brings to the development of very short and thin hair with a reduction of the anagen phase and epithelial and mesenchymal compartments dimensions. It’s been recently discovered that ADSC are able to induce hair growth of immunosuppressed animals in vitro and in vivo. In this case, stem cells isolated from adipose tissue are tested for their ability to induce hair regeneration
ONGOING

Research of new active molecules for tissue regeneration in case of myocardial infarction.

Hyaluronan mixed esters of butyric and retinoic acid (HBR) are able to induce cardiogenesis and vasculogenesis either in vitro in mesenchymal cells isolated from the dental pulp, spinal cord and placenta or in vivo, in infracted rats. Mesenchymal stem cells transplantation derived from the placenta and treated with HBR increase capillary density in heart, normalizes ventricular functionality and reduces scar tissue. From a molecular point of view, HBR induces the expression of Smad proteins that play a key-role in the cardiogenesis processes. Successive studies showed how the injection of HBR into infracted rat hearts afforded substantial cardiovascular repair and recover of myocardial performance thanks to the recruitment of Stro-1 stem cells into a pro-angiogenic paracrine circuitry of angiogenetic factors. These findings may pave new perspectives in clinical studies for myocardial regeneration, without the need of stem cell transplantation. (Ventura et al. JBC 2007; / Lionetti et al., JBC 2010; / Maioli et al., PlosONE 2010).

► CLINICAL RESEARCH PROJECTS

Autologous adipose-derived stem cells for treatment of sistemic sclerosis.

Systemic sclerosis is a rare heterogeneous disease, characterized by progressive accumulation of fibrotic tissue on skin and internal organs. Autologous adipose-derived stem cells (ADSC) were expanded in vitro and administered to 6 patients with systemic sclerosis. ADSC were injected as a suspension in a solution containing hyaluronic acid. This treatment determined a significant improvement in tightening of the skin without complications, suggesting that ADSC are a potentially valuable source of cells for skin therapy (Scuderi et al., Cell Transplantation, in press).

Autologous adipose-derived stem cells for the regeneration of cutaneous tissue.

Thanks to their pluripotency, adipose-derived stem cells (ADSC) are one of the most promising populations of mesenchimal stem cells for regenerative medicine applications. Autologous, in-vitro expanded ADSC are administered to patients with severe cutaneous defects, such as burns, or aesthetic alterations, as stretch marks or cutaneous laxities. After treatment, morphological and functional analysis are performed to evaluate cutaneous regeneration.
ONGOING – University of Bologna

Autologous in-vitro expanded keratinocytes for reconstruction of oral mucosa.

Keratinocytes isolated from an oral mucosa biopsy are isolated and expanded in vitro till the formation of an epithelial patch. Patches are then applied to areas of the mouth where keratinized tissue is absent or incomplete.
ONGOING – University of Milan

Autologous in vitro-expanded keratinocytes for vaginal reconstruction in patients with Mayer-von Rokitansky-Kuster-Hauser syndrome.

Mayer-von Rokitansky-Kuster-Hauser syndrome is characterized by vaginal agenesis. A 28 years old woman with this syndrome underwent a successful autologous vaginal tissue transplantation. The transplanted patch was composed by in vitro-expanded keratinocytes obtained from a full-thickness mucosal biopsy from the vaginal vestibule (Benedetti Panici et al., Human Reproduction 2007) (Benedetti Panici et al., Human Reproduction 2007).