https://www.seas.upenn.edu/%7Edischer/pdfs/Cell_on_Gel-CELLpaper.pdf

Matrix elasticity directs stem cell lineage specification.

Future cell-based therapies such as tissue engineering will benefit from a source of autologous pluripotent stem cells. For mesodermal tissue engineering, one such source of cells is the bone marrow stroma. The bone marrow compartment contains several cell populations, including mesenchymal stem cells (MSCs) that are capable of differentiating into adipogenic, osteogenic, chondrogenic, and myogenic cells. However, autologous bone marrow procurement has potential limitations. An alternate source of autologous adult stem cells that is obtainable in large quantities, under local anesthesia, with minimal discomfort would be advantageous. In this study, we determined if a population of stem cells could be isolated from human adipose tissue. Human adipose tissue, obtained by suction-assisted lipectomy (i.e., liposuction), was processed to obtain a fibroblast-like population of cells or a processed lipoaspirate (PLA). These PLA cells can be maintained in vitro for extended periods with stable population doubling and low levels of senescence. Immunofluorescence and flow cytometry show that the majority of PLA cells are of mesodermal or mesenchymal origin with low levels of contaminating pericytes, endothelial cells, and smooth muscle cells. Finally, PLA cells differentiate in vitro into adipogenic, chondrogenic, myogenic, and osteogenic cells in the presence of lineage-specific induction factors. In conclusion, the data support the hypothesis that a human lipoaspirate contains multipotent cells and may represent an alternative stem cell source to bone marrow-derived MSCs.

/pdf/multilineage-cells-from-human-adipose-tissue-implications-4z32vwpf0q.pdf

Multilineage cells from human adipose tissue: implications for cell-based therapies.

Much of the work conducted on adult stem cells has focused on mesenchymal stem cells (MSCs) found within the bone marrow stroma. Adipose tissue, like bone marrow, is derived from the embryonic mesenchyme and contains a stroma that is easily isolated. Preliminary studies have recently identified a putative stem cell population within the adipose stromal compartment. This cell population, termed processed lipoaspirate (PLA) cells, can be isolated from human lipoaspirates and, like MSCs, differentiate toward the osteogenic, adipogenic, myogenic, and chondrogenic lineages. To confirm whether adipose tissue contains stem cells, the PLA population and multiple clonal isolates were analyzed using several molecular and biochemical approaches. PLA cells expressed multiple CD marker antigens similar to those observed on MSCs. Mesodermal lineage induction of PLA cells and clones resulted in the expression of multiple lineage-specific genes and proteins. Furthermore, biochemical analysis also confirmed lineage-specific activity. In addition to mesodermal capacity, PLA cells and clones differentiated into putative neurogenic cells, exhibiting a neuronal-like morphology and expressing several proteins consistent with the neuronal phenotype. Finally, PLA cells exhibited unique characteristics distinct from those seen in MSCs, including differences in CD marker profile and gene expression.

/pdf/human-adipose-tissue-is-a-source-of-multipotent-stem-cells-18jo72s52v.pdf

Human Adipose Tissue Is a Source of Multipotent Stem Cells

We report here that cells co-purifying with mesenchymal stem cells--termed here multipotent adult progenitor cells or MAPCs--differentiate, at the single cell level, not only into mesenchymal cells, but also cells with visceral mesoderm, neuroectoderm and endoderm characteristics in vitro. When injected into an early blastocyst, single MAPCs contribute to most, if not all, somatic cell types. On transplantation into a non-irradiated host, MAPCs engraft and differentiate to the haematopoietic lineage, in addition to the epithelium of liver, lung and gut. Engraftment in the haematopoietic system as well as the gastrointestinal tract is increased when MAPCs are transplanted in a minimally irradiated host. As MAPCs proliferate extensively without obvious senescence or loss of differentiation potential, they may be an ideal cell source for therapy of inherited or degenerative diseases.

/pdf/pluripotency-of-mesenchymal-stem-cells-derived-from-adult-200s4qlizf.pdf

Pluripotency of mesenchymal stem cells derived from adult marrow

Additive manufacturing, otherwise known as three-dimensional (3D) printing, is driving major innovations in many areas, such as engineering, manufacturing, art, education and medicine. Recent advances have enabled 3D printing of biocompatible materials, cells and supporting components into complex 3D functional living tissues. 3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues. Addressing these complexities requires the integration of technologies from the fields of engineering, biomaterials science, cell biology, physics and medicine. 3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures. Other applications include developing high-throughput 3D-bioprinted tissue models for research, drug discovery and toxicology.

3D bioprinting of tissues and organs

Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.

http://science.sciencemag.org/content/sci/284/5411/143.full.pdf

Multilineage Potential of Adult Human Mesenchymal Stem Cells

Adult Human Mesenchymal Stem Cell Differentiation to the Osteogenic or Adipogenic Lineage Is Regulated by Mitogen-activated Protein Kinase

Stem cells are the focus of intense interest from a growing, multidisciplinary community of investigators with tools for isolating and characterizing these elusive cell types. This volume, which features contributions from many of the world's leading laboratories, provides a broad and authoritative basis for understanding the biology of stem cells and the excitement about their potential for clinical exploitation. It should be a useful work of reference for investigators in embryology, hematology, and neurobiology, and their collaborators in the emerging field of regenerative medicine.

Stem Cell Biology

An inhalation device is provided with a mechanism to assure patient compliance with a drug dosage regimen. The control mechanism includes a controller (24), a timer (26), an actuator (28) and a signalling device (30). The controller (24) is programmed or preset with a time and dosage schedule for the drug to be delivered. For example, the controller (24) may be programmed to allow for two puffs from an MDI every eight hours. The actuator (28) operates in conjunction with the timer (26) and prevents the inhalation device from being actuated after the programmed dosage has been administered at the prescribed interval. The actuator (28) could be an electronically controlled valve (58) or pawl (66) arrangement or other suitable mechanism. The signaling device (30) provides an audible, visual or tactile sensation during the time period prescribed for administration of the drug so that the patient is reminded to inhale his or her medicine at the prescribed time intervals. The history of actuation, non-actuation, and improper attempts at actuation can all be recorded and analyzed off-site at a later by a physician, pharmacist, or other authorized health care professional.

Inhalation device with a dose-timer, an actuator mechanism, and patient compliance monitoring means

Methods and devices using non-autologous mesenchymal stem cells comprising treating a recipient in need thereof with an effective amount of non-autologous mesenchymal stem cells, including methods and preparations for treating and regenerating connective tissue and enhancing bone marrow engraftment in an individual; and for using genetically engineered allogeneic human mesenchymal stem cells that carry within them genes of interest particularly for the expression of physiologically or pharmacologically active proteins in gene therapy for correction of genetic disorders or “rebuilding” proteins important in tissue repair.

Daniel R. Marshak

Papers

Multilineage Potential of Adult Human Mesenchymal Stem Cells

Adult Human Mesenchymal Stem Cell Differentiation to the Osteogenic or Adipogenic Lineage Is Regulated by Mitogen-activated Protein Kinase

Stem Cell Biology

Inhalation device with a dose-timer, an actuator mechanism, and patient compliance monitoring means

Uses for non-autologous mesenchymal stem cells