Adult tissue resident or somatic stem cells

Adult tissue resident or somatic stem cells

Stem cells resident in the di ff erent tissues and organs are responsible for providing replacements for specialised cells that have reached the end of their functional lifespan either through natural attrition or because of damage and disease. In certain tissues and organs, notably the bone marrow and gut, stem cells regularly divide and di ff erentiate into specialised cells to replace senescent or damaged cells in the blood and the gastrointestinal mucosa, respectively . Stem cells in other organs, such as the heart or central nervous system, are less able to e ff ect repair or replacement. SSCs have the capacity to di ff erentiate into a limited number of specialised cell types (multipotent); among the best characterised types are haemato poietic stem cells. In tissue engineering and regenerative medi cine, mesenchymal stem or stromal cell (MSC) populations are widely described but have been more di ffi cult to characterise, particularly in terms of stem cell attrib utes relating to clinical use. Mesenchymal stem and stromal cells 1 Building on earlier observations in the 1960s relating to bone marrow-derived cell populations, in the 1990s the term ‘mesenchymal stem cell’ (MSC) was used in relation to therapy , based on observations that some of these cells, under the right conditions, could di ff erentiate into cell types relating to muscu 2 loskeletal, adipose and other tissues. In 2005 the International Society for Cellular Therapy (now the International Society for Cell and Gene Therapy; ISCT) proposed that these cells be termed multipotent ‘mesenchymal stromal cells’ with the same abbreviation MSC, and that the term mesenchymal stem demonstrate stem cell activity by clearly stated criteria’. They 4 went on to describe minimum criteria in 2006 : adherence to plastic, expression of certain surface markers (CD105, CD73 and CD90) but a lack of expression of others (CD45, CD34, CD14 or CD11b, CD79 α or CD19 and HLA-DR) and, finally , the ability to di ff erentiate into osteoblasts, adipocytes and chondroblasts in vitro , often described by authors as trilineage di ff erentiation. The importance of nomenclature relates to the mechanism by which such cells might achieve a clinical e ff ect. The earlier term mesenchymal ‘stem’ cell implies that cells directly con - tribute to re pair and regeneration by di ff erentiation, whereas using the term ‘stromal’ can encompass paracrine and secre - tory behaviour, in which cells are envisaged to work with other cells to influence the outcome of repair and regenera tion ( Figure 4.3 ) . As a consequence, the term mesenchymal ‘stem’ cell has been highlighted as a cause of potential confusion, - whereby pa tients might wrongly infer that the cell constitutes 5,6 - a ‘stem cell therapy’. In 2019, the ISCT gave continued sup - port for the term mesenchymal stromal cell but recommended that it be: supplemented with the tissue source of the cell; intended unless rigorous evidence for stemness exits; associ - 7 ated with robust functional assays demonstrating properties. A further consideration is the manufacture and delivery of such cells. MSCs can be isolated from bone marrow (iliac crest aspiration) or from subcutaneous fat (liposuction/lipoaspira - tion). Cells can be delivered at the point of care, using bedside systems, or isolated in vitro on the basis of their adherence to plastic and subsequently further characterised. Therefore, they - can be used shortly after extraction or after expansion of their numbers by in vitro culture. Furthermore, MSCs can be di ff er - entiated into the desired lineage in vitro by addition of suitable growth factors and chemicals. The wide variety of cell type, source and manufacturing process represent important opportunities for treatment.

Cell culture Osteoblast Chondrocyte Adipocyte In vitro trilineage differentiation Figure 4.3 Proposed characteristics of mesenchymal stromal cells relevant to tissue engineering and regenerative medicine. Mesenchymal stromal cell Interaction with in /f_l ammatory and immune processes B-cell Macrophage Natural killer cell Dendritic cell T cell

the understanding of which will be greatly improved by molecular biology techniques and functional assay . In terms of agreed nomenclature, a report on consensus has described key parameters in the abbreviation DOSES: D /uni00A0 – /uni00A0 donor, O /uni00A0 – /uni00A0 origin tissue, S /uni00A0 – /uni00A0 separation method, E /uni00A0 – /uni00A0 exhibited characteristics, 8 S /uni00A0 – /uni00A0 site of delivery . The relative ease of cell acquisition has meant that autologous MSCs have been used in clinical settings and they represent a great opportunity for new treatment development. Before widespread adoption, more translational research is required to understand and refine the therapeutic mechanism of action and conduct well-designed clinical trials to establish the evidence of e ff ectiveness. Adult tissue resident or somatic stem cells

Stem cells resident in the di ff erent tissues and organs are responsible for providing replacements for specialised cells that have reached the end of their functional lifespan either through natural attrition or because of damage and disease. In certain tissues and organs, notably the bone marrow and gut, stem cells regularly divide and di ff erentiate into specialised cells to replace senescent or damaged cells in the blood and the gastrointestinal mucosa, respectively . Stem cells in other organs, such as the heart or central nervous system, are less able to e ff ect repair or replacement. SSCs have the capacity to di ff erentiate into a limited number of specialised cell types (multipotent); among the best characterised types are haemato poietic stem cells. In tissue engineering and regenerative medi cine, mesenchymal stem or stromal cell (MSC) populations are widely described but have been more di ffi cult to characterise, particularly in terms of stem cell attrib utes relating to clinical use. Mesenchymal stem and stromal cells 1 Building on earlier observations in the 1960s relating to bone marrow-derived cell populations, in the 1990s the term ‘mesenchymal stem cell’ (MSC) was used in relation to therapy , based on observations that some of these cells, under the right conditions, could di ff erentiate into cell types relating to muscu 2 loskeletal, adipose and other tissues. In 2005 the International Society for Cellular Therapy (now the International Society for Cell and Gene Therapy; ISCT) proposed that these cells be termed multipotent ‘mesenchymal stromal cells’ with the same abbreviation MSC, and that the term mesenchymal stem demonstrate stem cell activity by clearly stated criteria’. They 4 went on to describe minimum criteria in 2006 : adherence to plastic, expression of certain surface markers (CD105, CD73 and CD90) but a lack of expression of others (CD45, CD34, CD14 or CD11b, CD79 α or CD19 and HLA-DR) and, finally , the ability to di ff erentiate into osteoblasts, adipocytes and chondroblasts in vitro , often described by authors as trilineage di ff erentiation. The importance of nomenclature relates to the mechanism by which such cells might achieve a clinical e ff ect. The earlier term mesenchymal ‘stem’ cell implies that cells directly con - tribute to re pair and regeneration by di ff erentiation, whereas using the term ‘stromal’ can encompass paracrine and secre - tory behaviour, in which cells are envisaged to work with other cells to influence the outcome of repair and regenera tion ( Figure 4.3 ) . As a consequence, the term mesenchymal ‘stem’ cell has been highlighted as a cause of potential confusion, - whereby pa tients might wrongly infer that the cell constitutes 5,6 - a ‘stem cell therapy’. In 2019, the ISCT gave continued sup - port for the term mesenchymal stromal cell but recommended that it be: supplemented with the tissue source of the cell; intended unless rigorous evidence for stemness exits; associ - 7 ated with robust functional assays demonstrating properties. A further consideration is the manufacture and delivery of such cells. MSCs can be isolated from bone marrow (iliac crest aspiration) or from subcutaneous fat (liposuction/lipoaspira - tion). Cells can be delivered at the point of care, using bedside systems, or isolated in vitro on the basis of their adherence to plastic and subsequently further characterised. Therefore, they - can be used shortly after extraction or after expansion of their numbers by in vitro culture. Furthermore, MSCs can be di ff er - entiated into the desired lineage in vitro by addition of suitable growth factors and chemicals. The wide variety of cell type, source and manufacturing process represent important opportunities for treatment.

Cell culture Osteoblast Chondrocyte Adipocyte In vitro trilineage differentiation Figure 4.3 Proposed characteristics of mesenchymal stromal cells relevant to tissue engineering and regenerative medicine. Mesenchymal stromal cell Interaction with in /f_l ammatory and immune processes B-cell Macrophage Natural killer cell Dendritic cell T cell

the understanding of which will be greatly improved by molecular biology techniques and functional assay . In terms of agreed nomenclature, a report on consensus has described key parameters in the abbreviation DOSES: D /uni00A0 – /uni00A0 donor, O /uni00A0 – /uni00A0 origin tissue, S /uni00A0 – /uni00A0 separation method, E /uni00A0 – /uni00A0 exhibited characteristics, 8 S /uni00A0 – /uni00A0 site of delivery . The relative ease of cell acquisition has meant that autologous MSCs have been used in clinical settings and they represent a great opportunity for new treatment development. Before widespread adoption, more translational research is required to understand and refine the therapeutic mechanism of action and conduct well-designed clinical trials to establish the evidence of e ff ectiveness. Adult tissue resident or somatic stem cells

Stem cells resident in the di ff erent tissues and organs are responsible for providing replacements for specialised cells that have reached the end of their functional lifespan either through natural attrition or because of damage and disease. In certain tissues and organs, notably the bone marrow and gut, stem cells regularly divide and di ff erentiate into specialised cells to replace senescent or damaged cells in the blood and the gastrointestinal mucosa, respectively . Stem cells in other organs, such as the heart or central nervous system, are less able to e ff ect repair or replacement. SSCs have the capacity to di ff erentiate into a limited number of specialised cell types (multipotent); among the best characterised types are haemato poietic stem cells. In tissue engineering and regenerative medi cine, mesenchymal stem or stromal cell (MSC) populations are widely described but have been more di ffi cult to characterise, particularly in terms of stem cell attrib utes relating to clinical use. Mesenchymal stem and stromal cells 1 Building on earlier observations in the 1960s relating to bone marrow-derived cell populations, in the 1990s the term ‘mesenchymal stem cell’ (MSC) was used in relation to therapy , based on observations that some of these cells, under the right conditions, could di ff erentiate into cell types relating to muscu 2 loskeletal, adipose and other tissues. In 2005 the International Society for Cellular Therapy (now the International Society for Cell and Gene Therapy; ISCT) proposed that these cells be termed multipotent ‘mesenchymal stromal cells’ with the same abbreviation MSC, and that the term mesenchymal stem demonstrate stem cell activity by clearly stated criteria’. They 4 went on to describe minimum criteria in 2006 : adherence to plastic, expression of certain surface markers (CD105, CD73 and CD90) but a lack of expression of others (CD45, CD34, CD14 or CD11b, CD79 α or CD19 and HLA-DR) and, finally , the ability to di ff erentiate into osteoblasts, adipocytes and chondroblasts in vitro , often described by authors as trilineage di ff erentiation. The importance of nomenclature relates to the mechanism by which such cells might achieve a clinical e ff ect. The earlier term mesenchymal ‘stem’ cell implies that cells directly con - tribute to re pair and regeneration by di ff erentiation, whereas using the term ‘stromal’ can encompass paracrine and secre - tory behaviour, in which cells are envisaged to work with other cells to influence the outcome of repair and regenera tion ( Figure 4.3 ) . As a consequence, the term mesenchymal ‘stem’ cell has been highlighted as a cause of potential confusion, - whereby pa tients might wrongly infer that the cell constitutes 5,6 - a ‘stem cell therapy’. In 2019, the ISCT gave continued sup - port for the term mesenchymal stromal cell but recommended that it be: supplemented with the tissue source of the cell; intended unless rigorous evidence for stemness exits; associ - 7 ated with robust functional assays demonstrating properties. A further consideration is the manufacture and delivery of such cells. MSCs can be isolated from bone marrow (iliac crest aspiration) or from subcutaneous fat (liposuction/lipoaspira - tion). Cells can be delivered at the point of care, using bedside systems, or isolated in vitro on the basis of their adherence to plastic and subsequently further characterised. Therefore, they - can be used shortly after extraction or after expansion of their numbers by in vitro culture. Furthermore, MSCs can be di ff er - entiated into the desired lineage in vitro by addition of suitable growth factors and chemicals. The wide variety of cell type, source and manufacturing process represent important opportunities for treatment.

Cell culture Osteoblast Chondrocyte Adipocyte In vitro trilineage differentiation Figure 4.3 Proposed characteristics of mesenchymal stromal cells relevant to tissue engineering and regenerative medicine. Mesenchymal stromal cell Interaction with in /f_l ammatory and immune processes B-cell Macrophage Natural killer cell Dendritic cell T cell

the understanding of which will be greatly improved by molecular biology techniques and functional assay . In terms of agreed nomenclature, a report on consensus has described key parameters in the abbreviation DOSES: D /uni00A0 – /uni00A0 donor, O /uni00A0 – /uni00A0 origin tissue, S /uni00A0 – /uni00A0 separation method, E /uni00A0 – /uni00A0 exhibited characteristics, 8 S /uni00A0 – /uni00A0 site of delivery . The relative ease of cell acquisition has meant that autologous MSCs have been used in clinical settings and they represent a great opportunity for new treatment development. Before widespread adoption, more translational research is required to understand and refine the therapeutic mechanism of action and conduct well-designed clinical trials to establish the evidence of e ff ectiveness.