Table of Contents  
Year : 2021  |  Volume : 8  |  Issue : 4  |  Page : 360-362

Stem cell for vascular disease: Past, present, and future

Department of Vascular and Endovascular Surgery, Care Hospital, Hyderabad, Telangana, India

Date of Submission29-Nov-2021
Date of Acceptance29-Nov-2021
Date of Web Publication9-Dec-2021

Correspondence Address:
Pritee Sharma
Department of Vascular and Endovascular Surgery, Care Hospital, Hyderabad, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijves.ijves_128_21

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How to cite this article:
Sharma P. Stem cell for vascular disease: Past, present, and future. Indian J Vasc Endovasc Surg 2021;8:360-2

How to cite this URL:
Sharma P. Stem cell for vascular disease: Past, present, and future. Indian J Vasc Endovasc Surg [serial online] 2021 [cited 2022 Aug 15];8:360-2. Available from:

Peripheral arterial disease is a chronic inflammatory condition that results in clogged blood vessels. Patients with critical ischemia with a reconstructable disease can be subjected to endovascular balloon angioplasty, stenting, and/or bypass surgery. However, there are a significant number of peripheral vascular disease patients who cannot be helped by such interventions due to the presence of life-threatening comorbidities or diffuse nature of underlying vascular pathology. The quest for alternative revascularization strategies or therapeutic angiogenesis started on the background of research done by a prolific developmental biologist.

  Stem cell Biology Top

Stem cells are unspecialized cells of human body that can differentiate into any cell of an organ and have the ability of self-renewal.

A blastocyst forms after sperm and ovum fusion. Human embryonic stem cells are derived from the inner cell mass of the blastocyst. The pluripotency of these stem cells allows them to form any cell of the organism. After differentiation into one of the germ layers (endoderm, mesoderm, and ectoderm), under certain physiological conditions, they occur all over the organism as undifferentiated cells, and under certain physiological conditions, they can differentiate into specialized cells [Figure 1]. These cells facilitate healing, growth, and replacement of the cells lost daily due to wear and tear of tissues.
Figure 1: Stem cell Biology. Available from:

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  Amphibia, Vertebrate, and Mammal Experiments Top

Robert William Briggs and Thomas J. King in 1952 were successful in transferring undifferentiated embryonic nuclei to an embryonic cell that stimulated organ development. This nuclear transplantation paved the way for later research into somatic cell nuclear transfer and understanding of stem cells.[1]

In 1962, Sir John B Gurdon removed the nucleus of a fertilized egg cell from a frog and replaced it with the nucleus of a cell taken from a tadpole's intestine. This experiment showed that a nucleus can promote the formation of a differentiated intestine cell and a mature cell contains the genetic information needed to form all types of cells.[2]

This eventual identification of reprogramming molecules and mechanisms facilitated a route toward the application of this knowledge for potential stem cell therapies. In 2006, Takahashi and Yamanaka discovered that induced pluripotent stem cells can be generated from mouse embryonic fibroblasts and adult mouse tail-tip fibroblasts by retrovirus-mediated transfection of four transcription factors (Oct-3/4, Sox2, KLF4, and c-Myc).[3],[4]

One year later, this experiment was successful in humans, and Yu et al. were successful in deriving induced pluripotent stem cell lines from human somatic cells.[5]

Sir John B. Gurdon and Shinya Yamanaka have been awarded the Nobel Prize in Physiology/Medicine (2012) for the discovery that “mature cells can be reprogrammed to become pluripotent” [Figure 2] and [Figure 3].
Figure 2: Sir John B. Gurdon. Courtesy: Sir John B. Gurdon – Facts.[14]

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Figure 3: Shinya Yamanaka. Courtesy: Shinya Yamanaka – Facts.[15]

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In the past decade, clinical trials [Table 1] in peripheral arterial disease have shown varied results due to discrepancies related to stem cell source, mode of delivery, patient selection criteria, and duration of study and outcomes. The discrepancy could possibly be due to the difference in responsiveness to angiogenic stimuli in humans as compared to animal models. The increased levels of vascular endothelial growth factors (not decreased) in peripheral arterial disease patients were observed by Blann et al.,[13] an indirect evidence of potential defect in vascular endothelial growth factor responsiveness. The animal models used in experimental studies often do not have ongoing vascular disease and hence may not mimic the decreased angiogenic responsiveness.
Table 1: Clinical trials

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  Potential Therapeutic Application Top

The ability of stem cells for both self-renewal and directed differentiation can influence endogenous vascular stem cells behavior to prevent initiation and disease progression. Exogenous stem cell delivery can promote disease reversal and heal tissue injury. Evidence suggests that stem cells have a role in neointimal formation and initiation of vascular calcification in atherosclerosis. Hence, identifying appropriate cellular targets (e.g., RNA sequencing and epigenetic profiling for vascular stem cell screening) and understanding underlying regulatory mechanisms will facilitate the development of therapies for vascular disease and also can be used as a source for fabricating vascular grafts.

Continuously evolving knowledge about vascular stem cell biology will lead to the discovery of diagnostic and therapeutic strategies to combat vascular diseases and promote regeneration.


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Conflicts of interest

There are no conflicts of interest.

  References Top

Briggs R, King TJ. Transplantation of living nuclei from blastula cells into enucleated frogs' eggs. Proc Natl Acad Sci U S A 1952;38:455-63.  Back to cited text no. 1
Gurdon JB. The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. Development 1962;10:622-40.  Back to cited text no. 2
Sommer CA, Mostoslavsky G. Experimental approaches for the generation of induced pluripotent stem cells. Stem Cell Res Ther 2010;1:26.  Back to cited text no. 3
Takahashi K, Yamanaka S. Induced pluripotent stem cells in medicine and biology. Development 2013;140:2457-61.  Back to cited text no. 4
Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 2007;318:1917-20.  Back to cited text no. 5
Kim SW, Han H, Chae GT, Lee SH, Bo S, Yoon JH, et al. Successful stem cell therapy using umbilical cord blood-derived multipotent stem cells for Buerger's disease and ischemic limb disease animal model. Stem Cells 2006;24:1620-6.  Back to cited text no. 6
Dash NR, Dash SN, Routray P, Mohapatra S, Mohapatra PC. Targeting nonhealing ulcers of lower extremity in human through autologous bone marrow-derived mesenchymal stem cells. Rejuvenation Res 2009;12:359-66.  Back to cited text no. 7
Guiducci S, Porta F, Saccardi R, Guidi S, Ibba-Manneschi L, Manetti M, et al. Autologous mesenchymal stem cells foster revascularization of ischemic limbs in systemic sclerosis: A case report. Ann Intern Med 2010;153:650-4.  Back to cited text no. 8
Lu D, Chen B, Liang Z, Deng W, Jiang Y, Li S, et al. Comparison of bone marrow mesenchymal stem cells with bone marrow-derived mononuclear cells for treatment of diabetic critical limb ischemia and foot ulcer: A double-blind, randomized, controlled trial. Diabetes Res Clin Pract 2011;92:26-36.  Back to cited text no. 9
Lasala GP, Silva JA, Gardner PA, Minguell JJ. Combination stem cell therapy for the treatment of severe limb ischemia: Safety and efficacy analysis. Angiology 2010;61:551-6.  Back to cited text no. 10
Lasala GP, Silva JA, Minguell JJ. Therapeutic angiogenesis in patients with severe limb ischemia by transplantation of a combination stem cell product. J Thorac Cardiovasc Surg 2012;144:377-82.  Back to cited text no. 11
Lee HC, An SG, Lee HW, Park JS, Cha KS, Hong TJ, et al. Safety and effect of adipose tissue-derived stem cell implantation in patients with critical limb ischemia: A pilot study. Circ J 2012;76:1750-60.  Back to cited text no. 12
Blann AD, Lip GY, McCollum CN. Influence of the risk factors for atherosclerosis on levels of soluble adhesion molecules and endothelial markers in peripheral vascular disease. Thromb Haemost 2002;88:366-7.  Back to cited text no. 13
Nobel Prize Outreach AB 2021. Sun. 5 Dec 2021.  Back to cited text no. 14
Nobel Prize Outreach AB 2021. Sun. 5 Dec 2021.  Back to cited text no. 15


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]


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