Dr. Cassino is a Pittsburgh Tissue Engineering Initiative (PTEI) Post-Doctoral Fellow with a joint appointment in the Department of Orthopaedic Surgery at the University of Pittsburgh, and the Department of Mechanical Engineering at Carnegie Mellon University. Her multidisciplinary research combines cell biology and engineering to explore the effects of mechanical stimulation while concurrently controlling chemistry and scaffolding in vitro and in vivo to guide muscle derived stem cell differentiation toward the cardiac lineage. This work was done in collaboration with Dr Philip LeDuc's laboratory at Carnegie Mellon University. At the SCRC, Dr. Cassino was working with Lauren Drowley to investigate resistance to stress in human muscle-derived cells for application in myocardial infarct repair.

Mr. Corselli provides the laboratory with valuable experience in stem cell research with a focus on endothelial progenitor cells (EPCs), and bone marrow-derived multipotent stromal or mesenchymal stem cells.

He has isolated, characterized, and performed clinical scale expansion of cord blood-derived EPCs. He has also characterized peripheral blood EPCs isolated from subjects afflicted with myeloproliferative disorders.

Mr. Corselli has used bone marrow-derived multipotent stromal or mesenchymal stem cells to perform in vitro and in vivo studies on kidney regeneration/protection, and has carried out in vivo studies on the support of hematopoiesis after intra-bone co-injection with hematopoietic stem cells.

Dr. Corsi's main interests lay in studying the effect of BMP4 and mechanical stimulation on MDSCs. Her projects included the following:

• The investigation of the osteogenic potential of male and female MDSCs with BMP4 treatment, as well as the signaling pathways activated by BMP4.
• The effect of cyclic mechanical strain on the proliferation and osteogenic differentiation of MDSCs in vitro.
• Chondrogenic differentiation of male and female MDSCs when treated with BMP4.

As a Research Associate working toward her Ph.D. through the University of Paris, Mrs. Crisan worked on the identification and characterization of stem cells in human tissues during ontogeny and in the adult.

During her time here, her appointments included: University of Pittsburgh School of Medicine; Pediatrics, Children's Hospital of Pittsburgh; Pathology, Hillman Cancer Center.

"To advance stem cell research to the clinic, it will be necessary to extrapolate non-human stem cell studies to human stem cells and develop pre-clinical in vivo models. Stem cells derived from mouse muscle can participate in skeletal muscle regeneration in a dystrophy model. Duchenne muscular dystrophy is a common X-linked disease characterized by widespread muscle damage that invariably leads to paralysis and death. It affects 1 in 3500 boys and results in skeletal muscle fiber necrosis and degeneration. Ultimately the disease leads to cardiac and respiratory complications and affected individuals generally do not survive past their early twenties. Muscle-derived stem cells (MDSC) are capable of restoring the missing dystrophin protein in a muscular dystrophy mouse model. The aim of my work is to demonstrate the myogenic potential of different subpopulations isolated from human fetal skeletal muscle for the expression of membrane antigens CD133, CD56 and CD146, a population that could represent an alternative source of therapeutic stem cells. It is likely that these progenitors are recruited for muscle regeneration from a pool of circulating hematopoietic stem cells. In particular, a subpopulation of human muscle-derived stem cells expressing the CD133 antigen can differentiate into muscle, hematopoietic and endothelial cells when exposed to certain cytokines. CD133 is a 120-kDA glycosylated polypeptide expressed on a population of circulating human hematopoietic/endothelial progenitors and other stem cells. The function of CD133, which does not share homology with any previously described hematopoietic cell surface antigen, is not known. CD133+ cells can repopulate the bone marrow and differentiate into mature endothelial cells. These observations were extended to human circulating CD133+ cells from normal blood samples. When injected into skeletal tissues of scid/mdx dystrophic mice, human circulating CD133+ cells participate in muscle regeneration, and also replenish satellite cell compartment of the injected dystrophic muscle, causing a significant amelioration of skeletal muscle structure and function. The isolation and transplantation of more potent stem cells, such as CD133+/CD146+/CD34-/CD45- cells isolated from human muscle, will improve the outcome of cell therapy for muscular dystrophy. The primary goals of my project are 1) the characterization the expression of CD133 antigen in human fetal skeletal muscle, and 2) the isolation of CD133+/CD146+/CD34-/CD45- population from human fetal muscle and evaluate their myogenic potential in vitro and in vivo."

Dr. Liu's research interest focused primarliy on bone and cartilage engineering using muscle-derived stem cells. He sudied MDSCs that had been genetically engineered to express BMP-4 to provide an enhanced ability for bone and cartilage repair. He was also interested in the effects of mechanical stimulation on the osteogenic potential of MDSCs.

Masa is an orthopaedic surgeon from Nagoya, Japan. At the University of Pittsburgh Medical Center, Masa worked in muscle research as well as learning sports medicine and arthroscopic surgery techniques. Muscle regeneration after muscle injury or contusion, especially the effect of the antifibrotic agent suramin in healing in injured skeletal muscle, are areas in which he will experimented.

Dr. Okada is a visiting Japanese Research Fellow from Nagoya, Japan. He has many integrations within the group involving his surgical specialty on animal models. His current projects involve the use of human myoblasts for myocardial infarct repair in xenotransplantation studies.

Dr. Osawa is involved with research specifically relating to meniscus and meniscus regeneration.

Ms. Park is focused on stem cell bioogy using human embryonic stem (hES) cells and human fetal placenta cells to perform research relating to the hematopoietic and vascular endothelial lineages. Tea Soon's main projects include the following:
1. Differentiation of hES cells using a human embryoid (hEB) system with special emphasis on hamangioblast populations.
2. Transplantation of differentiating hES cells into chick embryo systems in order to document hematopoietic and endothelial cell engraftment potential.
3. Examination of the developmental potential of hEB cells expressing peri-vascular cell markers (e.g., CD146).
4. Lymphoid lineage differentiation of non-hematopoietic marker-expressing human fetal placenta cells.
5. Assessment of myogenic regenaration capacity of human fetal placenta blood vessel cells.

Dr. Péault is recognized for his research on the identification, characterization and purification of several categories of human stem cells, and has recently been appointed as a Professor in the Departments of Pediatrics and Cell Biology at the University of Pittsburgh. At the SCRC, he directs the EVA Cells Lab.

Dr. Péault’s laboratory has principally studied the ontogeny of the blood and vascular systems, but has also approached, in these models, the development and regeneration of other tissues and organs, including skin, airway, and lymph nodes. Since becoming part of the Children’s Hospital of Pittsburgh , Dr. Péault has also been engaged in the prospective identification, purification, and characterization of multipotent progenitor cells present in adult human tissues. Primarily, his group has demonstrated that these cells are present in adult organs in close association with the walls of blood vessels, which explains their ubiquitous presence throughout the body. These cells, which notably exhibit robust myogenic and cardiomyogenic potentials, may be of outstanding clinical interest since they can be extracted from such convenient sources as the bone marrow, muscle, and even adipose tissue before being extensively expanded in culture.

Mr. Uehara worked at the SCRC in the Bone and Cartilage Injuries lab.

Dr. Bo Zheng mainly focused on the isolation and characterization of human myogenic-endothelial cells, which are vascular-associated muscle derived stem cells arising from adult human skeletal muscle. She also investigated the regeneration capacity of these human cells after intramuscular injection into skeletal muscle. These studies were the first to identify a population of cells in human skeletal muscle that co-express markers of myogenic cells and endothelial cells, and, moreover, that endothelial marker-expressing cells have a dramatic myogenic potential in vivo. This primary study also demonstrated the fact that myo-endothelial clones can be isolated from human skeletal muscle using FACS. More importantly, it was discovered that single-cell-derived clonal populations spontaneously differentiated into myocytes, endothelial cells, smooth muscle cells, and neural cells. These clonal cells also differentiated into adipocytes, chondrocytes, osteoblasts, cardiomyocytes, and myotubes under specific conditions in vitro. Further studies are under way to investigate the multilineage potential of these cells in vivo, including their potential use in bone and cartilage repair, as well as muscle and cardiac regeneration.

Dr. Zheng's study of murine adipose-derived adult stem cells (ADAS) demonstrated that such cells can undergo multilineage differentiation in vitro and display superior ability to form bone and cartilage in vivo, suggesting that these cells may serve as a new source for bone and cartilage repair using cell-based gene therapy. This work was published by Tissue Engineering ( 2006; 12(7): 1891-1901).

Dr. Zheng recieved funding from The Pittsburgh Foundation for her research project: Long-term observation of human adipose-derived stem cell differentiation into osteogenic and chondrogenic lineages as a means of improving bone and cartilage healing. The amount was $5,000.00 (Ref.#:M2007-0126).