Granted Patent
B2
US 12,312,600 · App. 17/441,690 · Granted May 27, 2025
Methods for obtaining induced smooth muscle cells
Assignee:
INNOVACELL GMBH
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Abstract
The present invention relates to methods for obtaining induced smooth muscle cells (iSMCs), iSMCs, iSMCs for use in a method of treating a disease or disorder or for use in tissue engineering, and the use of skeletal muscle derived cells for obtaining iSMCs.
Claims (13)
1. An in vitro or ex vivo method for obtaining induced smooth muscle cells (iSMCs), the method comprising the steps of:
(a) obtaining skeletal muscle-derived cells from a subject;
(b) transdifferentiating skeletal muscle-derived cells by cultivating the cells in a medium containing TGF-beta and heparin to obtain iSMCs,
wherein the skeletal muscle-derived cells are myogenic progenitor cells (MPCs) characterized by the positive expression of CD56 and desmin, and the negative expression of CD3.
2. The method according to claim 1 , wherein the iSMCs obtained in step (b) are non-fusion competent and/or characterized by the positive expression of aSMA, CD49a, and CD146.
3. The method according to claim 1 , wherein the iSMCs obtained from MPCs in step (b) are characterized by the positive expression of aSMA, CD49a, desmin, CD56, and CD146, and the negative expression of CD3.
4. The method according to claim 1 , wherein after step (a) a step (a1) is conducted comprising proliferating the skeletal muscle-derived cells.
5. The method according to claim 1 , wherein step (b) is conducted for one to six days.
6. The method according to claim 1 , wherein TGF-beta in step (b) of claim 1 is:
(i) TGFb1, TGFb2 and/or TGFb3, or
( 11 ) TGFb1 and/or TGFb3, or
iii) TGFb1.
7. The method of claim 1 , wherein the TGF-beta is TGFb1.
Assignments (2)
CHANGE OF NAME
Recorded Feb 25, 2025
From: INNOVACELL AG
To: INNOVACELL GMBH
Reel/Frame 070318/0026 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 21, 2023
From: THURNER, MARCO; MARKSTEINER, RAINER
To: INNOVACELL AG
Reel/Frame 063397/0086 →
Priority Claims (1)
EP 19164574
· Mar 22, 2019
· regional
Continuity (1)
References Cited (126)
US 5667778A
· Atala
· 1997
[cited by examiner]
US 20050079606A1
· Tamaki et al.
· 2005
[cited by applicant]
US 20070264712A1
· Savant-Bhonsale
· 2007
[cited by applicant]
US 20080213231A1
· Oh et al.
· 2008
[cited by applicant]
US 20090155221A1
· Payne et al.
· 2009
[cited by applicant]
US 20090269310A1
· Le Ricousse et al.
· 2009
[cited by applicant]
US 20230285467A1
· Turner et al.
· 2023
[cited by applicant]
CN 101310013A
· 2008
[cited by applicant]
CN 103230415A
· 2013
[cited by applicant]
CN 106350480A
· 2017
[cited by applicant]
EP 2120976B1
· 2009
[cited by applicant]
EP 2206774
· 2010
[cited by applicant]
EP 3056562A1
· 2016
[cited by examiner]
JP 2009508511A
· 2009
[cited by applicant]
WO WO0178754
· 2001
[cited by applicant]
WO WO03027281
· 2003
[cited by applicant]
WO WO2007010858A1
· 2007
[cited by applicant]
WO WO2007106200
· 2007
[cited by applicant]
WO WO2008153813
· 2008
[cited by applicant]
WO WO2014044867
· 2014
[cited by applicant]
WO WO2019115790A1
· 2019
[cited by applicant]
WO WO2020193460
· 2020
[cited by applicant]
WO WO2023012334A1
· 2023
[cited by applicant]
Shudo et al., “Isolation and trans-differentiation of mesenchymal stromal cells into smooth muscle cells: Utility and applicability for cell-sheet engineering”. Cytotherapy. Apr. 2016 ; 18(4): 510-517. (Year: 2016).
[cited by examiner]
Park et al., “Functional expression of smooth muscle-specific ion channels in TGF-β-treated human adipose-derived mesenchymal stem cells”. Am J Physiol Cell Physiol. 2013;305(4):1-12. (Year: 2013).
[cited by examiner]
Gong et al., “Influence of Culture Medium on Smooth Muscle Cell Differentiation from Human Bone Marrow-Derived Mesenchymal Stem Cells”. Tissue Eng Part A. Feb. 2009;15(2):319-330 (Year: 2009).
[cited by examiner]
Villiers et al. (Villiers et al., “Adipose Derived Stem Cells and Smooth Muscle Cells: Implications for Regenerative Medicine”. Stem Cell Rev and Rep 5, pp. 256-265 (Year: 2009).
[cited by examiner]
Sandison et al., “Heterogeneity in the Proliferative Capacity of Smooth Muscle Cells (SMCs)”. FASEB; 29(1): 1-2 (Year: 2015).
[cited by examiner]
Orlandi et al., “Proliferative Activity and a-Smooth Muscle Actin Expression in Cultured Rat Aortic Smooth Muscle Cells Are Differently Modulated by Transforming Growth Factor-β1 and Heparin”. Experimental Cell Research…
[cited by examiner]
Abrahamsson, Hasse. “Treatment options for patients with severe gastroparesis.”
[cited by applicant]
Abujarour, Ramzey, et al. “Myogenic differentiation of muscular dystrophy-specific induced pluripotent stem cells for use in drug discovery.”
[cited by applicant]
Al-Ali, S., et al. “Correlation between gross anatomical topography, sectional sheet plastination, microscopic anatomy and endoanal sonography of the anal sphincter complex in human males.”
[cited by applicant]
Bajpai, Vivek K., et al. “Functional vascular smooth muscle cells derived from human induced pluripotent stem cells via mesenchymal stem cell intermediates.”
[cited by applicant]
Belkin, Vladimir M., Alexey M. Belkin, and Victor E. Koteliansky. “Human smooth muscle VLA-1 integrin: purification, substrate specificity, localization in aorta, and expression during development.”
[cited by applicant]
Bohl, Jaime L., Elie Zakhem, and Khalil N. Bitar. “Successful treatment of passive fecal incontinence in an animal model using engineered biosphincters: a 3-month follow-up study.”
[cited by applicant]
Capetanaki, Yassemi, Derek J. Milner, and G. Weitzer. “Desmin in muscle formation and maintenance: knockouts and consequences.”
[cited by applicant]
Dash, Biraja C., et al. “Tissue-engineered vascular rings from human iPSC-derived smooth muscle cells.”
[cited by applicant]
Dominici, M et al. “Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.”
[cited by applicant]
Espagnolle, Nicolas et al. “CD146 expression on mesenchymal stem cells is associated with their vascular smooth muscle commitment.”
[cited by applicant]
Freshney, R. Ian. “Primary Culture.” In:
[cited by applicant]
Frudinger, A et al. “Autologous skeletal-muscle-derived cell injection for anal incontinence due to obstetric trauma: a 5-year follow-up of an initial study of 10 patients.”
[cited by applicant]
Frudinger, A et al. “Muscle-derived cell injection to treat anal incontinence due to obstetric trauma: pilot study with 1 year follow-up.”
[cited by applicant]
Frudinger, Andrea et al. “Skeletal muscle-derived cell implantation for the treatment of sphincter-related faecal incontinence.”
[cited by applicant]
Gharaibeh, Burhan, et al. “Isolation of a slowly adhering cell fraction containing stem cells from murine skeletal muscle by the preplate technique.”
[cited by applicant]
Goode, Patricia S et al. “Prevalence and correlates of fecal incontinence in community-dwelling older adults.”
[cited by applicant]
Huard, J et al. “Muscle-derived cell-mediated ex vivo gene therapy for urological dysfunction.”
[cited by applicant]
Iivanainen, A et al. “Primary structure and expression of a novel human laminin α4 chain.”
[cited by applicant]
International Search Report and Written Opinion issued in International Application No. PCT/EP2018/085015, mailed Feb. 18, 2019.
[cited by applicant]
International Search Report and Written Opinion issued in International Application No. PCT/EP2020/057940, mailed Apr. 22, 2020.
[cited by applicant]
Jung, Yunjoon et al. “Concise review: Induced pluripotent stem cell-derived mesenchymal stem cells: progress toward safe clinical products.”
[cited by applicant]
Krauss, Robert S et al. “Embracing change: striated-for-smooth muscle replacement in esophagus development.”
[cited by applicant]
Lecourt, Séverine et al. “Characterization of distinct mesenchymal-like cell populations from human skeletal muscle in situ and in vitro.”
[cited by applicant]
Li, Yanhui et al. “Smooth Muscle Progenitor Cells Derived From Human Pluripotent Stem Cells Induce Histologic Changes in Injured Urethral Sphincter.”
[cited by applicant]
Lu, A., et al. “Isolation of myogenic progenitor populations from Pax7-deficient skeletal muscle based on adhesion characteristics.”
[cited by applicant]
Lu, Shing-Hwa et al. “Characterization of smooth muscle differentiation of purified human skeletal muscle-derived cells.”
[cited by applicant]
McHugh, K M. “Molecular analysis of smooth muscle development in the mouse.”
[cited by applicant]
Meng, Jinhong et al. “Contribution of human muscle-derived cells to skeletal muscle regeneration in dystrophic bost mice.”
[cited by applicant]
Meyer, Isuzu, and Holly E Richter. “Impact of fecal incontinence and its treatment on quality of life in women.”
[cited by applicant]
Mimura, Toshiki et al. “Diagnostic evaluation of patients with faecal incontinence at a specialist institution.”
[cited by applicant]
Niessen, Petra et al. “Smoothelin-a is essential for functional intestinal smooth muscle contractility in mice.”
[cited by applicant]
Office Action and Search Report issued in Russian Application No. 2020120580/10(035099), dated Jun. 10, 2022. English Translation.
[cited by applicant]
Park, Jung Sik, et al. “Isolation of neural precursor cells from skeletal muscle tissues and their differentiation into neuron-like cells.”
[cited by applicant]
Park, Won Sun et al. “Functional expression of smooth muscle-specific ion channels in TOF-β(1)-treated human adipose-derived mesenchymal stem cells.”
[cited by applicant]
Popescu, L M et al. “Caveolae in smooth muscles: nanocontacts.”
[cited by applicant]
Qu, Zhuqing, et al. “Development of approaches to improve cell survival in myoblast transfer therapy.”
[cited by applicant]
Quander, Carline R et al. “Prevalence of and factors associated with fecal incontinence in a large community study of older individuals.”
[cited by applicant]
Qu-Petersen, Zhuqing et al. “Identification of a novel population of muscle stem cells in mice: potential for muscle regeneration.”
[cited by applicant]
Ramkumar, D, and K S Schulze. “The pylorus.”
[cited by applicant]
Rando and Blau. “Primary mouse myoblast purification, characterization, and transplantation for cell-mediated gene therapy.”
[cited by applicant]
Rao, Satish S C. “Pathophysiology of adult fecal incontinence.”
[cited by applicant]
Rochlin, Kate et al. “Myoblast fusion: when it takes more to make one.”
[cited by applicant]
Romaniszyn, Michał, et al. “Implantation of autologous muscle-derived stem cells in treatment of fecal incontinence: results of an experimental pilot study.”
[cited by applicant]
Sanders, K M. “Regulation of smooth muscle excitation and contraction.”
[cited by applicant]
Sharifiaghdas, Farzaneh et al. “Isolation of human adult stem cells from muscle biopsy for future treatment of urinary incontinence.”
[cited by applicant]
Skuk, Daniel et al. “Intramuscular transplantation of myogenic cells in primates: importance of needle size, cell number, and injection volume.”
[cited by applicant]
Sturgill, Elizabeth R., et al. “Biosynthesis of the major brain gangliosides GD1a and GT1b.”
[cited by applicant]
Syverud, Brian C., et al. “Isolation and purification of satellite cells for skeletal muscle tissue engineering.”
[cited by applicant]
Thurner, Marco et al. “Development of an in vitro potency assay for human skeletal muscle derived cells.”
[cited by applicant]
Thurner, Marco et al. “Generation of myogenic progenitor cell-derived smooth muscle cells for sphincter regeneration.”
[cited by applicant]
Torrente, Y et al. “Intraarterial injection of muscle-derived CD34(+)Sca-1(+) stem cells restores dystrophin in mdx mice.”
[cited by applicant]
Trébol, Jacobo et al. “Stem cell therapy for faecal incontinence: Current state and future perspectives.”
[cited by applicant]
Vaizey, C J et al. “Primary degeneration of the internal anal sphincter as a cause of passive faecal incontinence.”
[cited by applicant]
Van de Rijn, M et al. “CD34 expression by gastrointestinal tract stromal tumors,”
[cited by applicant]
Van Eys, Guillaume J et al. “Smoothelin in vascular smooth muscle cells.”
[cited by applicant]
Wang, Gang et al. “Origin and differentiation of vascular smooth muscle cells.”
[cited by applicant]
Wang, Jennifer Y, and Maher A Abbas. “Current management of fecal incontinence.”
[cited by applicant]
Wang, Jiaxu et al. “Multiple roles of alpha-smooth muscle actin in mechanotransduction.”
[cited by applicant]
Wang, Youwei et al. “Safety of mesenchymal stem cells for clinical application.”
[cited by applicant]
Wörl, Jürgen et al. “Deletion of Pax7 changes the tunica muscularis of the mouse esophagus from an entirely striated into a mixed phenotype.”
[cited by applicant]
Wright, Woodring E., and Jerry W. Shay. “Historical claims and current interpretations of replicative aging.”
[cited by applicant]
Yin, Hang et al. “Satellite cells and the muscle stem cell niche.”
[cited by applicant]
Krasnopolsky V.I. et al., “Stem cells in the treatment of patients with stress urinary incontinence”, Russian Bulletin of an Obstetrician-Gynecologist, 2007, No. 5, 44-47. English Abstract.
[cited by applicant]
Amend, B. et al., “Regeneration of Degenerated Urinary Sphincter Muscles: Improved Stem Cell-Based Therapies and Novel Imaging Technologies,”
[cited by applicant]
Pisani, D. F. et al., “Isolation of a Highly Myogenic CD34-Negative Subset of Human Skeletal Muscle Cells Free of Adipogenic Potential,”
[cited by applicant]
Search Report issued in counterpart Chilean Patent Application No. 202102169, issued Sep. 1, 2023.
[cited by applicant]
Huang, et al.,
[cited by applicant]
Office Action issued in Japanese Application No. 2020-533052, dated Aug. 9, 2022. With English Translation.
[cited by applicant]
Wen, J. et al., “Progress of stress urinary incontinence treatment by using stem cell,”
[cited by applicant]
Birbrair, A. et al., “Skeletal muscle neural progenitor cells exhibit properties of NG2-glia,”
[cited by applicant]
Frudinger, A. et al., “Skeletal Muscle-Derived Cell Implantation for the Treatment of Fecal Incontinence: A Randomized, Placebo-Controlled Study,”
[cited by applicant]
Hirai, H. et al., “Direct reprogramming of fibroblasts into Smooth Muscle-Like Cells with Defined Transcription Factors,”
[cited by applicant]
Incitti, T. et al., “Pluripotent stem cell-derived skeletal muscle fibers preferentially express myosin heavy-chain isoforms associated with slow and oxidative muscles,”
[cited by applicant]
International Search Report and Written Opinion issued in International Patent Application No. PCT/EP2022/072088, mailed Oct. 17, 2022.
[cited by applicant]
Ito, N. et al., “Direct reprogramming of fibroblasts into skeletal muscle progenitor cells by transcription factors enriched in undifferentiated subpopulation of satellite cells,”
[cited by applicant]
Jorge, J. et al., “Etiology and Management of Fecal Incontinence,” Dis Colon Rectum, 36.1 (1993): 77-96.
[cited by applicant]
Lebedeva, O. C. et al., “ ” 5.4 (2011): 37-45. No English translation available.
[cited by applicant]
Le Ricousse-Roussanne, S. et al., “Ex vivo generation of mature and functional human smooth muscle cells differentiated from skeletal myoblasts,”
[cited by applicant]
Li, B-J. et al., “Isolation, Culture and Identification of Porcine Skeletal Muscle Satellite Cells,”
[cited by applicant]
Messner, F. et al., ,,Myogenic progenitor cell transplantation for muscle regeneration following hindlimb ischemia and reperfusion,
[cited by applicant]
Miyagoe-Suzuki, Y. et al., “Skeletal muscle generated from induced pluripotent stem cells—induction and application,”
[cited by applicant]
Nolazco, G. et al., “Effect of muscle-derived stem cells on the restoration of corpora cavernosa smooth muscle and erectile function in the aged rat,”
[cited by applicant]
Notice of Allowance issued in Russian Patent Application No. 2021129050/10, dated Dec. 8, 2023 (English translation).
[cited by applicant]
Office Action issued in Japanese Patent Application No. 2021-552231, dated Jan. 4, 2023 (with English translation).
[cited by applicant]
Office Action issued in Chinese Patent Application No. 202080021489.4, dated Jan. 26, 2024 (with English translation).
[cited by applicant]
Opposition against European Patent No. 3724319, dated Jan. 9, 2024.
[cited by applicant]
Rao, S.S.C. et al., “Endpoints for Therapeutic Interventions in Fecal Incontinence: Small Step or Game Changer,”
[cited by applicant]
Seruya, M. et al., “Clonal Population or Adult Stem Cells: Life Span and Differentiation Potential,”
[cited by applicant]
Takahashi, K. et al., “Induction of pluripotent stem cells from adult human fibroblasts by defined factors,”
[cited by applicant]
Takahashi, K. et al., “Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors,”
[cited by applicant]
Tey, S-R. et al., “Coding Cell Identity of Human Skeletal Muscle Progenitor Cells Using Cell Surface Markers: Current Status and Remaining Challenges for Characterization and Isolation,”
[cited by applicant]
Wilschut, K. J. et al., “Approaches to isolate porcine skeletal muscle stem and progenitor cells,”
[cited by applicant]
Xuan, W. et al., “Pluripotent stem cell-induced skeletal muscle progenitor cells with givinostat promote myoangiogenesis and restore dystrophin in injured Duchenne dystrophic muscle,”
[cited by applicant]
Yamanaka, S., “Induction of pluripotent stem cells from mouse fibroblasts by four transcription factors,”
[cited by applicant]