본문 바로가기
KERD
논문KCI 등재

Combination stem cell therapy using dental pulp stem cells and human umbilical vein endothelial cells for critical hindlimb ischemia

2

조회

0

다운로드

0

인용

0

참고문헌

키워드

주제분류화학

초록

Narrowing of arteries supplying blood to the limbs provokescritical hindlimb ischemia (CLI). Although CLI results in irreversiblesequelae, such as amputation, few therapeutic options inducethe formation of new functional blood vessels. Based onthe proangiogenic potentials of stem cells, in this study, it wasexamined whether a combination of dental pulp stem cells(DPSCs) and human umbilical vein endothelial cells (HUVECs)could result in enhanced therapeutic effects of stem cells for CLIcompared with those of DPSCs or HUVECs alone. The DPSCs+HUVECs combination therapy resulted in significantly higherblood flow and lower ischemia damage than DPSCs or HUVECsalone. The improved therapeutic effects in the DPSCs+ HUVECsgroup were accompanied by a significantly higher number ofmicrovessels in the ischemic tissue than in the other groups. Invitro proliferation and tube formation assay showed that VEGFin the conditioned media of DPSCs induced proliferation andvessel-like tube formation of HUVECs. Altogether, our resultsdemonstrated that the combination of DPSCs and HUVECs hadsignificantly better therapeutic effects on CLI via VEGF-mediatedcrosstalk. This combinational strategy could be used to developnovel clinical protocols for CLI proangiogenic regenerative treatments.

Abstract

Narrowing of arteries supplying blood to the limbs provokescritical hindlimb ischemia (CLI). Although CLI results in irreversiblesequelae, such as amputation, few therapeutic options inducethe formation of new functional blood vessels. Based onthe proangiogenic potentials of stem cells, in this study, it wasexamined whether a combination of dental pulp stem cells(DPSCs) and human umbilical vein endothelial cells (HUVECs)could result in enhanced therapeutic effects of stem cells for CLIcompared with those of DPSCs or HUVECs alone. The DPSCs+HUVECs combination therapy resulted in significantly higherblood flow and lower ischemia damage than DPSCs or HUVECsalone. The improved therapeutic effects in the DPSCs+ HUVECsgroup were accompanied by a significantly higher number ofmicrovessels in the ischemic tissue than in the other groups. Invitro proliferation and tube formation assay showed that VEGFin the conditioned media of DPSCs induced proliferation andvessel-like tube formation of HUVECs. Altogether, our resultsdemonstrated that the combination of DPSCs and HUVECs hadsignificantly better therapeutic effects on CLI via VEGF-mediatedcrosstalk. This combinational strategy could be used to developnovel clinical protocols for CLI proangiogenic regenerative treatments.

참고문헌 (40)

  1. Sprengers RW, "Stem cell therapy in PAD", Eur J Vasc Endovasc Surg, 39(Suppl 1), pp.S38~S43 (2010)
  2. Johannesson A, "Incidence of lower-limb amputation in the diabetic and nondiabetic general population : a 10-year population-based cohort study of initial unilateral and contralateral amputations and reamputations", Diabetes Care, 32, pp.275~280 (2009)
  3. Adam DJ, "Bypass versus angioplasty in severe ischaemia of the leg(BASIL) : multicentre, randomised controlled trial", Lancet, 366, pp.1925~1934 (2005)
  4. Farber A, "The BESTCLI trial : a multidisciplinary effort to assess which therapy is best for patients with critical limb ischemia", Tech Vasc Interv Radiol, 17, pp.221~224 (2014)
  5. Kechagias A, "Limits of infrainguinal bypass surgery for critical leg ischemia in high-risk patients(Finnvasc score 3-4)", Ann Vasc Surg, 26, pp.213~218 (2012)
  6. Buckley RH, "A historical review of bone marrow transplantation for immunodeficiencies", J Allergy Clin Immunol, 113, pp.793~800 (2004)
  7. Martin I, "A relativity concept in mesenchymal stromal cell manufacturing", Cytotherapy, 18, pp.613~620 (2016)
  8. Al-Khaldi A, "Therapeutic angiogenesis using autologous bone marrow stromal cells : improved blood flow in a chronic limb ischemia model", Ann Thorac Surg, 75, pp.204~209 (2003)
  9. Diez-Tejedor E, "Reparative therapy for acute ischemic stroke with allogeneic mesenchymal stem cells from adipose tissue : a safety assessment : a phase II randomized, double-blind, placebo-controlled, single-center, pilot clinical trial", J Stroke Cerebrovasc Dis, 23, pp.2694~2700 (2014)
  10. Gupta PK, "A double blind randomized placebo controlled phase I", II study assessing the safety and efficacy of allogeneic bone marrow derived mesenchymal stem cell in critical limb ischemia, 2013, pp.11, 143~
  11. Vittorio O, "Endothelial differentiation of mesenchymal stromal cells : when traditional biology meets mechanotransduction", Integr Biol(Camb), 5, pp.291~299 (2013)
  12. Choi M, "Proangiogenic features of Wharton’s jelly-derived mesenchymal stromal", stem cells and their ability to form functional vessels, 2013, pp.45, 560~570
  13. Hoch AI, "Differentiation-dependent secretion of proangiogenic factors by mesenchymal stem cells", PLoS One, 7, pp.e35579~ (2012)
  14. Bronckaers A, "Angiogenic properties of human dental pulp stem cells", PLoS One, 8, pp.e71104~ (2013)
  15. Estrela C, "Mesenchymal stem cells in the dental tissues : perspectives for tissue regeneration", Braz Dent J, 22, pp.91~98 (2011)
  16. Leong WK, "Human adult dental pulp stem cells enhance poststroke functional recovery through non-neural replacement mechanisms", Stem Cells Transl Med, 1, pp.177~187 (2012)
  17. Mamidi MK, "Cell therapy in critical limb ischemia : current developments and future progress", Cytotherapy, 14, pp.902~916 (2012)
  18. Sakai K, "Human dental pulp-derived stem cells promote locomotor recovery after complete transection of the rat spinal cord by multiple neuro-regenerative mechanisms", J Clin Invest, 122, pp.80~90 (2012)
  19. Dissanayaka WL, "Coculture of dental pulp stem cells with endothelial cells enhances osteo-", odontogenic and angiogenic potential in vitro, 2012, pp.38, 454~463
  20. Dissanayaka WL, "The interplay of dental pulp stem cells and endothelial cells in an injectable peptide hydrogel on angiogenesis and pulp regeneration in vivo", 21, pp.550~563 (2015)
  21. Zhang Y, "DPSCs treated by TGF-β1 regulate angiogenic sprouting of three-dimensionally co-cultured HUVECs and DPSCs through VEGF-Ang-Tie2signaling", Stem Cell Res Ther, 12, pp.281~ (2021)
  22. Volponi AA, "Stem cellbased biological tooth repair and regeneration", Trends Cell Biol, 20, pp.715~722 (2010)
  23. Nam H, "Angiogenic capacity of dental pulp stem cell regulated by SDF-1alphaCXCR4 axis", Stem Cells Int, 2017, pp.8085462~ (2017)
  24. Gupta NK, "The current state of stem cell therapy for peripheral artery disease", Curr Cardiol Rep, 16, pp.447~ (2014)
  25. Liew A, "Therapeutic potential for mesenchymal stem cell transplantation in critical limb ischemia", Stem Cell Res Ther, 3, pp.28~ (2012)
  26. Bak S, "Delivery of a cell patch of cocultured endothelial cells and smooth muscle cells using thermoresponsive hydrogels for enhanced angiogenesis", Tissue Eng Part A, 22, pp.182~193 (2016)
  27. Ban DX, "Combination of activated Schwann cells with bone mesenchymal stem cells : the best cell strategy for repair after spinal cord injury in rats", Regen Med, 6, pp.707~720 (2011)
  28. Shi S, "Perivascular niche of postnatal mesenchymal stem cells in human bone marrow and dental pulp", J Bone Miner Res, 18, pp.696~704 (2003)
  29. Crisan M, "Perivascular cells for regenerative medicine", J Cell Mol Med, 16, pp.2851~2860 (2012)
  30. Lee KH, "Significant therapeutic effects of adult human multipotent neural cells on spinal cord injury", Stem Cell Res, 31, pp.71~78 (2018)
  31. Dissanayaka WL, "The interplay of dental pulp stem cells and endothelial cells in an injectable peptide hydrogel on angiogenesis and pulp regeneration in vivo", Tissue Eng Part A, 21, pp.550~563 (2015)
  32. Van Tongeren RB, "Intramuscular or combined intramuscular", intra-arterial administration of bone marrow mononuclear cells : a clinical trial in patients with advanced limb ischemia, 2008, pp.49, 51~58
  33. Reagan-Shaw S, "Dose translation from animal to human studies revisited", FASEB J, 22, pp.659~661 (2008)
  34. Flugelman MY, "Phase Ib safety, two-dose study of MultiGeneAngio in patients with chronic critical limb ischemia", Mol Ther, 25, pp.816~825 (2017)
  35. Lucitti JL, "Formation of the collateral circulation is regulated by vascular endothelial growth factor-A and a disintegrin and metalloprotease family members 10 and 17", Circ Res, 111, pp.1539~1550 (2012)
  36. Griffin M, "Genetically modified mesenchymal stem cells and their clinical potential in acute cardiovascular disease", Discov Med, 9, pp.219~223 (2010)
  37. Tateishi-Yuyama E, "Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells : a pilot study and a randomised controlled trial", Lancet, 360, pp.427~435 (2002)
  38. Jang S, "Induced pluripotent stem cell-derived endothelial cells : overview, current advances, applications, and future directions", Am J Pathol, 189, pp.502~512 (2019)
  39. Kuroda T, "Tumorigenicity studies for human pluripotent stem cell-derived products", Biol Pharm Bull, 36, pp.189~192 (2013)
  40. Ginsberg M, "Efficient direct reprogramming of mature amniotic cells into endothelial cells by ETS factors and TGFbeta suppression", Cell, 151, pp.559~575 (2012)

관련 논문AI추천

Co-culture of human umbilical vein endothelial cells with dental pulp-derived mesenchymal stem cells enhance the migration and differentiation potential to neural progenitor like cellsChan Hee Jo, Na Young Lee, Young Hoon Kang, Yun-Ho Kim치의학연구원 · Oral Biology Research2025 · 제49권 제4호Enhancement strategy for effective vascular regeneration following myocardial infarction through a dual stem cell approach김동빈, 장진아, Ban Kiwon, Cho Dong-Woo, Hwang Ji-Won, Jeon Seung Hwan, Kang Byeongmin, Kim Hyeok, Kim Hyo-Jin, Kim Jin-Ju, Lee Soon Min, Lee Sunghun, Moon Sung-Hwan, Park Bong Woo, Park Hun-Jun, Park Jae-Hyun, Park Soon-Jung, Sim Woo-Sup생화학분자생물학회 · Experimental and Molecular Medicine2022 · 제54권 Differentiation of CD31-Positive Vascular Endothelial Cells from Organoid Culture of Dental Pulp Stem Cells강정숙, 김형룡, 박재경, 서은진, 장일호, 정호임대한구강생물학회 · International Journal of Oral Biology2018 · 제43권 제2호Blood Vessel Regeneration using Human Umbilical Cord-derived Endothelial Progenitor Cells in Cyclophosphamide-treated Immune-deficient Mice조재진, 조태준, Byung-Chul Kang, Eu-Gene Park, Gene Lee, Soon-Keun Kwon, Yu-Jin Ko대한구강생물학회 · International Journal of Oral Biology2011 · 제36권 제3호Effect of hypoxia on angiogenesis-related proteins in human dental pulp cells김연, 김미경, 김소정, 김형준, 박현주, 배문경, 배수경, 조민지대한구강생물학회 · International Journal of Oral Biology2016 · 제41권 제3호유치치수유래 줄기세포치료제의 조직재생 임상적용 위한 가능성 고찰김병규, 김해원, 김형은, 신성진, 윤지영, 이승민, 이정환, 이해형대한치과의사협회 · 대한치과의사협회지2024 · 제62권 제3호

이 간행물의 다른 논문 (8건)