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Mechanisms of Action
with Supporting Data

General

The bladder can regenerate like nobody’s business and now we know why – Click Here

Bioelectric Signaling Controlled Protein Expressions

Patented and Patent Pending

Muscle Regeneration – Myogenesis

1. Follistatin.
2. Klotho.
3. SDF1 & PDGF.

Elasticity Regeneration

1. Tropoelastin

Nerve Regeneration

1. Sonic hedghog.
2. IGF1.
3. LIM.

Blood Vessel Regeneration – Angiogenesis

1. VEGF.
2. SDF1 & PDGF.
3. HIF1a.
4. eNOS.

Muscle Regeneration Supporting Data

Follistatin

Follistatin Improves Skeletal Muscle Healing after Injury and Disease through an Interaction with Muscle Regeneration, Angiogenesis, and Fibrosis – Click Here

Follistatin: A Novel Therapeutic for the Improvement of Muscle Regeneration – Click Here

Klotho

Klotho expression is a prerequisite for proper muscle stem cell function and regeneration of skeletal muscle – Click Here

’Longevity Protein’ Rejuvenates Muscle Healing in Old Mice – Click Here

SDF1 & PDGF

Stem cells migration during skeletal muscle regeneration – the role of Sdf-1/Cxcr4 and Sdf-1/Cxcr7 axis – Click Here

Stem cell recruitment after injury: lessons for regenerative medicine – Click Here

Coming soon wearables versions

Elasticity Regeneration

Tropoelastin Incorporation into a Dermal Regeneration – Click Here

Biomolecular Regulation of Elastic Matrix Regeneration and Repair – Click Here

Blood Vessel Regeneration – Angiogenesis

Electrical stimulation directly induces pre-angiogenic responses in vascular endothelial cells by signaling through VEGF receptors – Click Here

Establishment of a Simple and Practical Procedure Applicable to Therapeutic Angiogenesis – VEGF – Click Here

Stromal-Cell-Derived Factor-1 (SDF-1)/CXCL12 as Potential Target of Therapeutic Angiogenesis – Click Here

Nerve Regeneration

Regeneration of the Cavernous Nerve by Sonic Hedgehog – Click Here

Role of VIP and Sonic Hedgehog Signaling Pathways in Mediating Epithelial Wound Healing, Sensory Nerve Regeneration – Click Here

The multifunctional role of IGF-1 in peripheral nerve regeneration – Click Here

Insulin-like growth factor stimulates motor nerve regeneration – Click Here

Growth Hormone Improves Nerve Regeneration, Muscle Re-innervation, and Functional Outcomes After Chronic Denervation Injury – Click Here

Nerve Regeneration Pumped Up by Muscle Protein LIM – Click Here

BC-15 Composition

1. Stem cells – hypoxia treated.
2. Myoblasts.
3. Exosomes.
4. Stromal fraction.
5. PRF.
6. Amniotic fluid.
7. Oxygenated nanoparticles
8. Bladder matrix.
9. Nutrient hydrogel.
10. PRF.
11. Selected growth factors
12. Klotho.
13. Follistatin.
14. LIM protein.
15. Tropoelastin.

Current and Future Directions of Stem Cell Therapy for Bladder Dysfunction – Click Here

Application of Bladder Acellular Matrix in Urinary Bladder Regeneration: The State of the Art and Future Directions – Click Here

Regeneration of Bladder Urothelium, Smooth Muscle, Blood Vessels and Nerves Into an Acellular Tissue Matrix – Click Here

Bioengineering Approaches for Bladder Regeneration – Click Here

Exosomes secreted by urine-derived stem cells improve stress urinary incontinence by promoting repair of pubococcygeus muscle injury – Click Here

PRF Treatment for Painful Bladder Syndrome – Click Here

BC-15 Composition Components

1. Stem cells - hypoxia treated - MSCs, adipose derived, iPS
“Myogenic differentiation of mesenchymal stem cells for muscle regeneration in urinary tract”
o   https://pubmed.ncbi.nlm.nih.gov/23924474/
·      “Bladder Transplantation of Amniotic Fluid Stem Cell may Ameliorate Bladder Dysfunction After Focal Cerebral Ischemia in Rat”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442832/
·      “Effect of amniotic fluid stem cell transplantation on the recovery of bladder dysfunction in spinal cord-injured rats”
o   https://www.nature.com/articles/s41598-020-67163-7
·       “The basis of muscle regeneration” Specifically section 3 “The Phase of Regeneration, Remodeling, and Maturation”
o   https://www.hindawi.com/journals/ab/2014/612471/
·      “Muscle stem cells in developmental and regenerative myogenesis”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872152/
·      “Role of Stem Cells and Extracellular Matrix in the Regeneration of Skeletal Muscle”
o   https://www.intechopen.com/books/muscle-cell-and-tissue-current-status-of-research-field/role-of-stem-cells-and-extracellular-matrix-in-the-regeneration-of-skeletal-muscle
1. Stem cells - hypoxia treated - MSCs, adipose derived, iPS
“Myogenic differentiation of mesenchymal stem cells for muscle regeneration in urinary tract”
o   https://pubmed.ncbi.nlm.nih.gov/23924474/
·      “Bladder Transplantation of Amniotic Fluid Stem Cell may Ameliorate Bladder Dysfunction After Focal Cerebral Ischemia in Rat”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442832/
·      “Effect of amniotic fluid stem cell transplantation on the recovery of bladder dysfunction in spinal cord-injured rats”
o   https://www.nature.com/articles/s41598-020-67163-7
·       “The basis of muscle regeneration” Specifically section 3 “The Phase of Regeneration, Remodeling, and Maturation”
o   https://www.hindawi.com/journals/ab/2014/612471/
·      “Muscle stem cells in developmental and regenerative myogenesis”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872152/
·      “Role of Stem Cells and Extracellular Matrix in the Regeneration of Skeletal Muscle”
o   https://www.intechopen.com/books/muscle-cell-and-tissue-current-status-of-research-field/role-of-stem-cells-and-extracellular-matrix-in-the-regeneration-of-skeletal-muscle
2. Myoblasts
·      “Myoblast” Defined
o   https://www.biologyonline.com/dictionary/myoblast#:~:text=Myoblasts%20are%20the%20embryonic%20precursors,1
·      Another definition
o   sciencedirect.com/topics/medicine-and-dentistry/myoblast
·      “Preliminary results of myoblast injection into the urethra and bladder wall: a possible method for the treatment of stress urinary incontinence and impaired detrusor contractility” –Huard
o   https://pubmed.ncbi.nlm.nih.gov/10797585/
3. Exosomes

N/A

4. Stromal fraction
·      “Autologous and heterotopic transplantation of adipose stromal vascular fraction ameliorates stress urinary incontinence in rats with simulated childbirth trauma”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6147152/
·      “Construction of a vascularized bladder with autologous adipose-derived stromal vascular fraction cells combined with bladder acellular matrix via tissue engineering”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6886281/
·      “Human Adipose-Derived and Amniotic Fluid-Derived Stem Cells: A Preliminary In Vitro Study Comparing Myogenic Differentiation Capability”
o   ncbi.nlm.nih.gov/pmc/articles/PMC5882157/
·      “Verification of mesenchymal stem cell injection therapy for interstitial cystitis in a rat model”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907861/
·      “The adipose tissue stromal vascular fraction secretome enhances the proliferation but inhibits the differentiation of myoblasts”
o   https://stemcellres.biomedcentral.com/articles/10.1186/s13287-018-1096-6
·      “IL-4 and SDF-1 Increase Adipose Tissue-Derived Stromal Cell Ability to Improve Rat Skeletal Muscle Regeneration”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246596/
·      “Potential of adipose-derived stem cells in muscular regenerative therapies”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4499759/
5. PRF

N/A

6. Amniotic fluid
·      “Amniotic Fluid: Not Just Fetal Urine Anymore”
o   https://www.nature.com/articles/7211290
·      “Bladder Transplantation of Amniotic Fluid Stem Cell may Ameliorate Bladder Dysfunction After Focal Cerebral Ischemia in Rat”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442832/
·      “Effect of amniotic fluid stem cell transplantation on the recovery of bladder dysfunction in spinal cord-injured rats”
o   https://www.nature.com/articles/s41598-020-67163-7
·      “Human Adipose-Derived and Amniotic Fluid-Derived Stem Cells: A Preliminary In Vitro Study Comparing Myogenic Differentiation Capability”
o   ncbi.nlm.nih.gov/pmc/articles/PMC5882157/
·      “Embryology, Amniotic Fluid”
o   https://www.ncbi.nlm.nih.gov/books/NBK541089/
7. Oxygenated nanoparticles
·      “O2-generating MnO2 nanoparticles for enhanced photodynamic therapy of bladder cancer by ameliorating hypoxia”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817106/
·      “Nanotechnology in bladder cancer: current state of development and clinical practice”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562431/
·      “Size dependent translocation and fetal accumulation of gold nanoparticles from maternal blood in the rat”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4445676/
·      “Functional muscle recovery with nanoparticle-directed M2 macrophage polarization in mice”
o   https://www.pnas.org/content/115/42/10648
·      “Internalization and fate of silica nanoparticles in C2C12 skeletal muscle cells: evidence of a beneficial effect on myoblast fusion”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340375/
·      “Functional muscle recovery with nanoparticle-directed M2 macrophage polarization in mice”
o   https://www.pnas.org/content/pnas/115/42/10648.full.pdf
8. Bladder matrix
·      “Bioengineering Approaches for Bladder Regeneration”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032229/
·      “Co-delivery of micronized urinary bladder matrix damps regenerative capacity of minced muscle grafts in the treatment of volumetric muscle loss injuries”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5645132/
·      “Effect of amniotic fluid stem cell transplantation on the recovery of bladder dysfunction in spinal cord-injured rats”
o   https://www.nature.com/articles/s41598-020-67163-7
·      “Amniotic therapeutic biomaterials in urology: current and future applications”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673810/
·      “New Amniotic Membrane Based Biocomposite for Future Application in Reconstructive Urology”
o   https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146012
·      “Co-delivery of micronized urinary bladder matrix damps regenerative capacity of minced muscle grafts in the treatment of volumetric muscle loss injuries”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5645132/
·      “Current Methods for Skeletal Muscle Tissue Repair and Regeneration”
o   https://www.hindawi.com/journals/bmri/2018/1984879/
·      “Role of Stem Cells and Extracellular Matrix in the Regeneration of Skeletal Muscle”
o   https://www.intechopen.com/books/muscle-cell-and-tissue-current-status-of-research-field/role-of-stem-cells-and-extracellular-matrix-in-the-regeneration-of-skeletal-muscle
9. Nutrient hydrogel
·      “Hydrogel biomaterials and their therapeutic potential for muscle injuries and muscular dystrophies”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805959/
·      “Bioengineering Approaches for Bladder Regeneration”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032229/
·      “Injectable scaffold materials differ in their cell instructive effects on primary human myoblasts”
o   https://journals.sagepub.com/doi/full/10.1177/2041731417717677
·      “Capillary-Like Network Formation by Human Amniotic Fluid-Derived Stem Cells Within Fibrin/Poly(Ethylene Glycol) Hydrogels”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394886/
·      “Hydrogels for Skeletal Muscle Regeneration”
o   https://link.springer.com/article/10.1007/s40883-019-00146-x
·      “Photopolymerizable Hydrogel-Encapsulated Fibromodulin-Reprogrammed Cells for Muscle Regeneration”
o   https://www.liebertpub.com/doi/10.1089/ten.tea.2020.0026
·      “Advances in biomaterials for skeletal muscle engineering and obstacles still to overcome”
o   https://www.sciencedirect.com/science/article/pii/S2590006420300296
10. Selected growth factors
·      “Growth Factors for Skeletal Muscle Tissue Engineering”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5130097/
·      “Skeletal Myogenic Differentiation of Urine-Derived Stem Cells and Angiogenesis Using Microbeads Loaded with Growth Factors”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3513922/
·      “Growth Factors for Skeletal Muscle Tissue Engineering”
o   https://www.karger.com/Article/FullText/444671
·      “Efficient myoblast expansion for regenerative medicine use”
o   https://www.spandidos-publications.com/10.3892/ijmm.2014.1763
·      “A role for FGF-6 in skeletal muscle regeneration”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC316448/
·      “The factors present in regenerating muscles impact bone marrow-derived mesenchymal stromal/stem cell fusion with myoblasts”
o   https://stemcellres.biomedcentral.com/articles/10.1186/s13287-019-1444-1
·      “Tissue Therapy: Implications of Regenerative Medicine for Skeletal Muscle”
o   https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/muscle-regeneration
·      “Embryology, Amniotic Fluid”
o   https://www.ncbi.nlm.nih.gov/books/NBK541089/
·      “Amniotic fluid: Source of trophic factors for the developing intestine”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4753188/
·      “Applications of Amniotic Membrane and Fluid in Stem Cell Biology and Regenerative Medicine”
o   https://www.hindawi.com/journals/sci/2012/721538/
·       
11. Klotho
·      “Skeletal muscle as a regulator of the longevity protein, Klotho”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4060456/
·      “Klotho, stem cells, and aging”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4531025/
·      “Klotho expression is a prerequisite for proper muscle stem cell function and regeneration of skeletal muscle”
o   https://skeletalmusclejournal.biomedcentral.com/articles/10.1186/s13395-018-0166-x
·      “Klotho expression is a prerequisite for proper muscle stem cell function and regeneration of skeletal muscle” (Not a duplicate)
o   https://pubmed.ncbi.nlm.nih.gov/29973273/
·      “The Anti-Aging Role of Klotho in Skeletal Muscle Regeneration”
o   https://grantome.com/grant/NIH/R01-AG052978-01A1
·      “Skeletal muscle as a regulator of the longevity protein, Klotho”
o   https://www.frontiersin.org/articles/10.3389/fphys.2014.00189/full
·      “Regulation of amniotic fluid volume: insights derived from amniotic fluid volume function curves”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6230884/
·      “Anhydramnios in the Setting of Renal Malformations: The National Institutes of Health Workshop Summary”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5970061/
12. Follistatin
·      “Metabolic profiling of follistatin overexpression: a novel therapeutic strategy for metabolic diseases”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5875402/
·      “Follistatin Improves Skeletal Muscle Healing after Injury and Disease through an Interaction with Muscle Regeneration, Angiogenesis, and Fibrosis”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3157209/
·      “Inhibiting Myostatin With Follistatin Improves the Success of Myoblast Transplantation in Dystrophic Mice”
o   https://journals.sagepub.com/doi/pdf/10.3727/096368908784153913
·      “Follistatin improves skeletal muscle healing after injury and disease through an interaction with muscle regeneration, angiogenesis, and fibrosis”
o   https://pubmed.ncbi.nlm.nih.gov/21689628/
·      “Deacetylase Inhibitors Increase Muscle Cell Size by Promoting Myoblast Recruitment and Fusion through Induction of Follistatin”
o   https://www.cell.com/fulltext/S1534-5807(04)00107-8
·      “Overexpression of Follistatin in Human Myoblasts Increases Their Proliferation and Differentiation, and Improves the Graft Success in SCID Mice”
o   https://journals.sagepub.com/doi/pdf/10.3727/096368909X470865
·      “Inhibiting Myostatin with Follistatin Improves the Success of Myoblast Transplantation in Dystrophic Mice”
o   https://journals.sagepub.com/doi/abs/10.3727/096368908784153913
·      “Inhibin and activin in embryonic and fetal development in ruminants”
·      https://pubmed.ncbi.nlm.nih.gov/7623312/
·      “Imbalance of Amniotic Fluid Activin-A and Follistatin in Intraamniotic Infection, Inflammation, and Preterm Birth”
·      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287504/
13. LIM protein
·      “Muscle LIM protein promotes myogenesis by enhancing the activity of MyoD.”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC232327/
·      “Muscle LIM protein/CSRP3: a mechanosensor with a role in autophagy”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981024/
·      “The LIM Protein, CRP1, Is a Smooth Muscle Marker”
o   https://anatomypubs.onlinelibrary.wiley.com/doi/pdf/10.1002/(SICI)1097-0177(199903)214:3%3C229::AID-AJA6%3E3.0.CO;2-S
·      “Muscle LIM protein/CSRP3: a mechanosensor with a role in autophagy”
o   https://www.nature.com/articles/cddiscovery201514
·      “Muscle Lim Protein: master regulator of cardiac and skeletal muscle function”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660132/
·      “Muscle Lim Protein isoform negatively regulates striated muscle actin dynamics and differentiation”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4416226/
·      “Muscle LIM Protein Promotes Myogenesis by Enhancing the Activity of MyoD”
o   https://mcb.asm.org/content/mcb/17/8/4750.full.pdf
·      “Muscle Lim Protein and myosin binding protein C form a complex regulating muscle differentiation”
o   https://www.sciencedirect.com/science/article/pii/S0167488917302264
·      “Amniotic fluid transcriptomics reflects novel disease mechanisms in fetuses with myelomeningocele”
o   https://pubmed.ncbi.nlm.nih.gov/28735706/
·      “Lim Mineralization Protein 3 Induces the Osteogenic Differentiation of Human Amniotic Fluid Stromal Cells through Kruppel-Like Factor-4 Downregulation and Further Bone-Specific Gene Expression”
o   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471036/
·      “Amniotic Fluid Protein Profiles of Intraamniotic Inflammatory Response to Ureaplasma spp. and Other Bacteria”
o   https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0060399
14. Tropoelastin
·      “Amniocentesis and Tropoelastin”
·      https://www.researchgate.net/topic/Amniocentesis~Tropoelastin/publications
·      “Tropoelastin-Coated Tendon Biomimetic Scaffolds Promote Stem Cell Tenogenic Commitment and Deposition of Elastin-Rich Matrix”
·      https://pubs.acs.org/doi/full/10.1021/acsami.9b04616
·      “Use of Placental Membranes for the Treatment of Chronic Diabetic Foot Ulcers”
·      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529081/
·      “Advances in biomimetic regeneration of elastic matrix structures”
·      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3551595/
·      “Urinary Bladder Contraction and Relaxation: Physiology and Pathophysiology”
·      https://journals.physiology.org/doi/full/10.1152/physrev.00038.2003
·      “Training differentially regulates elastin level and proteolysis in skeletal and heart muscles and aorta in healthy rats”
·      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874357/
·      “In vitro myogenesis induced by human recombinant elastin-like proteins”
·      https://pubmed.ncbi.nlm.nih.gov/26231915/
·      “Loss of miR-29 in Myoblasts Contributes to Dystrophic Muscle Pathogenesis”
·      https://www.cell.com/molecular-therapy-family/molecular-therapy/comments/S1525-0016(16)32546-1
·      “Skeletal Muscle Tissue Engineering: Methods to Form Skeletal Myotubes and Their Applications”
·      https://www.liebertpub.com/doi/10.1089/ten.teb.2013.0534
·      “Transcriptional profiling and regulation of the extracellular matrix during muscle regeneration”
·      https://journals.physiology.org/doi/full/10.1152/physiolgenomics.00056.2003