Compositions and methods for ameliorating tissue injury, enhancing liver regeneration and stem cell therapies

2:

• The method of claim 1, wherein:
• (a) the compound or composition capable of inhibiting or decreasing the expression or activity of the MMP protein, transcript and/or gene, optionally in a liver-selective manner, is or comprises:
• (1) a nucleic acid, and optionally the nucleic acid is an inhibitory nucleic acid comprising:
• an RNAi inhibitory nucleic acid molecule, a double-stranded RNA (dsRNA) molecule, a microRNA (mRNA), a small interfering RNA (siRNA), an antisense RNA, a short hairpin RNA (shRNA), or a ribozyme capable of capable of inhibiting or decreasing the expression or activity of the MMP protein, transcript and/or gene,
• (2) a peptide or polypeptide, wherein optionally the polypeptide is or comprises an antibody or fragment thereof or equivalent thereof, capable of specifically binding the MMP, and is capable of inhibiting or decreasing the activity of the MMP enzyme, transcript and/or gene, or
• (3) a small molecule, lipid, saccharide, nucleic acid or polysaccharide capable of inhibiting or decreasing the activity of the MMP enzyme, transcript and/or gene,
• wherein optionally the small molecule comprises prinomastat, marimastat, batimastat, cipemastat, ilomastat (also known as galardin), rebimastat, tanomastat or any combination thereof,
• (b) the compound or composition is formulated as a pharmaceutical composition, or is formulated for administration in vivo;
• or formulated for enteral or parenteral administration, or for oral, intravenous (IV) or intrathecal (IT) administration, wherein optionally the compound or formulation is administered orally, parenterally, by inhalation spray, nasally, topically, intrathecally, intrathecally, intracerebrally, epidurally, intracranially or rectally;
• wherein optionally the formulation or pharmaceutical composition is contained in or carried in a nanoparticle, a particle, a micelle or a liposome or lipoplex, a polymersome, a polyplex or a dendrimer;
• or
• (c) the compound or composition, or the formulation or pharmaceutical composition, is formulated as, or contained in, a nanoparticle, a liposome, a tablet, a pill, a capsule, a gel, a geltab, a liquid, a powder, an emulsion, a lotion, an aerosol, a spray, a lozenge, an aqueous or a sterile or an injectable solution, or an implant.

9:

• A method for:
• (i) enhancing an infused or exogenous progenitor cell, optionally a bone marrow endothelial progenitor cell, engraftment in an organ or a tissue, wherein optionally the organ or tissue is a heart, kidney, brain, muscle, bone, skin, trachea, arterial or venous blood vessels, intestine, spinal cord, lung, or a liver, by preventing or inhibiting proteolytic cleavage of a sdf1 in the organ or the tissue, thereby preserving the chemoattractant effect of the sdf1 and also preserving a bone marrow sdf1, thereby reducing release of an endogenous progenitor cell, optionally an endogenous bone marrow endothelial progenitor cell, from the bone marrow, to decrease competition for engraftment of the infused or exogenous progenitor cell by the endogenous progenitor cell,
• (ii) reducing release of endogenous progenitor cells, optionally sprocs, from the bone marrow, and/or
• (iii) preventing or inhibiting proteolytic cleavage of the sdf1 systemically;
• comprising:
• (a) administering to an individual in need thereof a compound or composition capable of inhibiting or decreasing the expression or activity of a matrix metalloproteinase (MMP) in a systemic manner, or treating the organ or tissue with the compound or composition capable of inhibiting or decreasing the expression or activity of the MMP, and optionally the treatment is in a perfusion bath;
• or
• (b) (1) providing a compound or composition capable of inhibiting or decreasing the expression or activity of a matrix metalloproteinase (MMP) in a systemic manner,
• wherein optionally the matrix metalloproteinase (MMP) is a matrix metalloproteinase-9 (MMP-9), and optionally the MMP inhibition is MMP-9 specific,
• and optionally the MMP is MMP-1, MMP-2, MMP-3, MMP-11, or MMP-13, and optionally the MMP inhibition is MMP-1, MMP-2, MMP-3, MMP-11, or MMP-13 specific;
• and
• (2) administering the compound or composition to the individual in need thereof,
• thereby
• (i) enhancing infused or exogenous progenitor cell, optionally bone marrow endothelial progenitor cell, engraftment in an organ or a tissue, wherein optionally the organ or tissue is a heart, kidney, brain, spinal cord, lung, or a liver, by preventing or inhibiting proteolytic cleavage of a sdf1 in the organ or the tissue, thereby preserving the chemoattractant effect of the sdf1 and also preserving a bone marrow sdf1, thereby reducing release of an endogenous progenitor cell, optionally an endogenous bone marrow endothelial progenitor cell, from the bone marrow, to decrease competition for engraftment of the infused or exogenous progenitor cell by the endogenous progenitor cell,
• (ii) reducing release of endogenous progenitor cells, optionally sprocs, from the bone marrow, and/or
• (iii) preventing or inhibiting proteolytic cleavage of the sdf1 systemically.

10:

• The method of claim 9, wherein:
• (a) the compound or composition capable of inhibiting or decreasing the expression or activity of the MMP protein, transcript and/or gene, optionally in an organ-selective manner, is or comprises:
• (1) a nucleic acid, and optionally the nucleic acid is an inhibitory nucleic acid comprising:
• an RNAi inhibitory nucleic acid molecule, a double-stranded RNA (dsRNA) molecule, a microRNA (mRNA), a small interfering RNA (siRNA), an antisense RNA, a short hairpin RNA (shRNA), or a ribozyme capable of capable of inhibiting or decreasing the expression or activity of the MMP protein, transcript and/or gene,
• (2) a peptide or polypeptide, wherein optionally the polypeptide is or comprises an antibody or fragment thereof or equivalent thereof, capable of specifically binding the MMP, and is capable of inhibiting or decreasing the activity of the MMP enzyme, transcript and/or gene, or
• (3) a small molecule, lipid, saccharide, nucleic acid or polysaccharide capable of inhibiting or decreasing the activity of the MMP enzyme, transcript and/or gene,
• wherein optionally the small molecule comprises prinomastat, marimastat, batimastat, cipemastat, ilomastat (also known as galardin), rebimastat, tanomastat or any combination thereof,
• (b) the compound or composition is formulated as a pharmaceutical composition, or is formulated for administration in vivo;
• or formulated for enteral or parenteral administration, or for oral, intravenous (IV) or intrathecal (IT) administration, wherein optionally the compound or formulation is administered orally, parenterally, by inhalation spray, nasally, topically, intrathecally, intrathecally, intracerebrally, epidurally, intracranially or rectally;
• wherein optionally the formulation or pharmaceutical composition is contained in or carried in a nanoparticle, a particle, a micelle or a liposome or lipoplex, a polymersome, a polyplex or a dendrimer;
• or
• (c) the compound or composition, or the formulation or pharmaceutical composition, is formulated as, or contained in, a nanoparticle, a liposome, a tablet, a pill, a capsule, a gel, a geltab, a liquid, a powder, an emulsion, a lotion, an aerosol, a spray, a lozenge, an aqueous or a sterile or an injectable solution, or an implant.