Designing Stem Cells As a Drug

Abstract

Stem cells have the ability to differentiate into various cell types, making them a promising therapeutic approach for a wide range of diseases. Stem cell therapy has shown great potential in treating cancer, autoimmune disorders, and degenerative diseases. However, the efficient differentiation of stem cells into the desired cell type, safety concerns, and optimal dosing and transplantation parameters remain major challenges. In this chapter, we discuss the potential of stem cells as a therapeutic approach, the challenges that need to be addressed, and the opportunities for future research. The chapter covers various types of stem cells, including embryonic stem cells, adult stem cells, and induced pluripotent stem cells, and their potential in treating different diseases. The key challenges include efficient differentiation, safety concerns, and optimal dosing and transplantation parameters. The chapter also discusses potential solutions to these challenges, including new differentiation protocols, safety evaluations, and optimization of transplantation parameters. Overall, stem cell therapy is a promising approach for many diseases, but further research is needed to optimize this approach and make it feasible for clinical use.

Introduction

Stem cells are a promising tool for regenerative medicine due to their ability to differentiate into multiple cell types. There are several types of stem cells, including embryonic stem cells (ESCs), adult stem cells (ASCs), and induced pluripotent stem cells (iPSCs), each with their own unique properties and potential applications.

The discovery of iPSCs by Yamanaka[1] in 2006 opened up new possibilities for personalized therapy using patient-specific cells. However, the use of stem cells for therapeutic purposes also presents several challenges that must be addressed, such as ensuring their safe and efficient differentiation into desired cell types, as well as determining optimal dosing and transplantation parameters. Embryonic stem cells are derived from the inner cell mass of blastocysts and have the ability to differentiate into any cell type in the body. Adult stem cells, on the other hand, are found in adult tissues such as bone marrow, adipose tissue, and blood, and have a more limited differentiation potential. iPSCs are generated by reprogramming adult cells to a pluripotent state using genetic manipulation, which allows them to differentiate into multiple cell types. While ESCs have traditionally been seen as the most versatile type of stem cell, recent research has shown that iPSCs can also differentiate into a wide range of cell types with similar efficiency.[2]

Stem cell therapy has shown great promise in treating a variety of diseases, including cancer, neurological disorders, and degenerative diseases such as Parkinson’s disease and diabetes. However, there are still significant challenges that must be overcome to make this approach feasible for clinical use. For example, one major challenge is the potential for transplanted stem cells to form tumors or other unwanted cell types. Another challenge is the efficient differentiation of stem cells into the desired cell type, which requires an understanding of the underlying molecular mechanisms.[3]

In this chapter, we will discuss the potential of stem cells as a therapeutic approach, the challenges that need to be addressed, and the opportunities for future research. We will also explore the different types of stem cells and their potential applications in regenerative medicine.

Ultimately, the success of stem cell therapy will depend on the ability to overcome these challenges and optimize the use of stem cells for therapeutic purposes.[4]

Adult stem cells are a type of stem cell found in various tissues of the body, such as bone marrow, adipose tissue, and blood. These cells have the ability to self-renew and differentiate into a limited range of cell types, making them a promising tool for regenerative medicine. ASCs have been studied extensively for their potential applications in tissue repair and regeneration, as well as for their role in maintaining tissue homeostasis and immune function.[5]

One of the main advantages of ASCs is their relative ease of isolation and expansion, which makes them a more accessible source of stem cells compared to ESCs. Adult stem cells have also been shown to be less immunogenic than other types of stem cells, which reduces the risk of rejection in transplantation. Additionally, ASCs have been used in clinical trials for various conditions, including cardiovascular disease, bone and cartilage defects, and neurological disorders.[6] Despite their promise, there are still several challenges that need to be addressed before ASCs can be widely used for therapeutic purposes. One major challenge is the efficient differentiation of ASCs into desired cell types, which requires a thorough understanding of the molecular mechanisms involved. Another challenge is the potential for ASCs to form tumors or other unwanted cell types, which must be carefully monitored and controlled.[7] We will explore the current state of research on ASCs, their potential applications in regenerative medicine, and the challenges that must be overcome to make this approach feasible for clinical use. We will also discuss the different types of ASCs, their properties, and potential applications, and the ongoing research efforts to improve their efficacy and safety.[8]

Embryonic stem cells are derived from the inner cell mass of blastocysts, which are early-stage embryos. These cells are pluripotent, meaning they have the ability to differentiate into any cell type in the body. Due to their unique properties, ESCs have the potential to revolutionize regenerative medicine and provide new treatments for a wide variety of diseases.[9]

Embryonic stem cells are undifferentiated cells that are derived from the inner cell mass of a blastocyst, which is a structure that forms in the early development of an embryo. They have the unique ability to differentiate into any type of cell in the body, including those of the nervous system, heart, liver, and pancreas. This pluripotent property makes them a valuable tool for regenerative medicine, tissue engineering, and drug discovery.[10]

One of the key advantages of ESCs is their ability to differentiate into any cell type in the body, making them a valuable tool for studying cell development and disease progression. Embryonic stem cells can also be cultured in large numbers, providing ample cell resources for research and potential treatments.[11]

Despite their potential benefits, there are ethical concerns with the use of ESCs, as their derivatives require the destruction of early-stage embryos. This has led to ongoing controversy regarding the use of ESCs in research and clinical practice.[12] Over the years, researchers have made significant advances in understanding the biology of ESCs and developing techniques for their isolation and differentiation. However, challenges still remain in the clinical translation of ESC-based therapies, such as teratoma formation and the risk of immune rejection.[13]

Embryonic stem cells have the potential to differentiate into any type of cell in the human body, making them a valuable tool for drug development and disease modeling.[14] The ability to create new drugs using ESCs is a promising avenue for treating a variety of diseases, including genetic disorders, cancer, and neurological disorders.[15] Induced pluripotent stem cells are a type of stem cell that can be generated from adult cells through a process called reprogramming.[16]

The discovery of iPSCs has revolutionized the field of regenerative medicine, as they offer a potentially limitless source of patient-specific cells for use in disease modeling, drug discovery, and cell-based therapies.[17] Induced pluripotent stem cells have the ability to differentiate into any cell type in the body, just like ESCs, but they do not require the use of embryos or oocytes, which raises ethical concerns.[18] Despite the many advantages of iPSCs, there are still challenges to be addressed, such as the potential for tumorigenesis and the efficiency and safety of the reprogramming process.[19] Stem cell therapy is an innovative approach to treating a variety of diseases and injuries by using stem cells to replace or repair damaged tissues and organs.[20] Stem cells are undifferentiated cells that have the ability to differentiate into different cell types in the body. Stem cell therapy holds great potential for regenerative medicine, as it can be used to treat a wide range of conditions, such as heart disease, diabetes, spinal cord injuries, and neurodegenerative diseases.[21]

There are different types of stem cells that can be used for therapy, including ESCs, iPSCs, and ASCs.[22] Despite the promising results of early clinical trials, there are still many challenges to be addressed in the field of stem cell therapy, such as the safety, efficacy, and ethical concerns surrounding the use of stem cells.[23] Stem cell therapy has the potential to revolutionize medicine by providing a way to regenerate and repair damaged tissues and organs. One of the most exciting applications of stem cell therapy is in the treatment of heart disease, which is a leading cause of death worldwide. Stem cells have been shown to have the ability to repair damaged heart tissue by differentiating into cardiomyocytes, the cells that make up the heart muscle.[24] Similarly, stem cells can be used to regenerate pancreatic beta cells in patients with diabetes, which could potentially lead to a cure for the disease.[25]

In addition to the therapeutic potential of stem cells, they are also valuable tools for drug discovery and disease modeling. Stem cells can be used to create disease models in the laboratory, which can help researchers better understand the underlying mechanisms of diseases and develop new therapies.[26] Stem cells are also being used to develop new drugs and to test the safety and efficacy of existing drugs.[27]

Despite the potential of stem cell therapy, there are still many challenges that need to be addressed. One of the major challenges is the risk of tumor formation, which can occur when stem cells differentiate in an uncontrolled manner.[28] Another challenge is the need to develop more efficient and cost-effective methods for producing large quantities of high-quality stem cells.[29] Furthermore, ethical concerns surrounding the use of ESCs continue to be a topic of debate.[30]

Stem cells have emerged as a promising therapeutic approach for a variety of diseases and injuries. They have the ability to self-renew and differentiate into specialized cell types, which makes them valuable for regenerating damaged tissue and organs.[31] Stem cells can be obtained from a variety of sources, including embryos, adult tissues, and iPSCs.[32]

One of the main advantages of stem cell therapy is its potential to treat conditions that currently have no effective treatment options. For example, stem cells have shown promise in treating neurodegenerative diseases such as Parkinson’s and Alzheimer’s.[33] They have also been used to treat spinal cord injuries, which were previously considered irreversible.[34] Another application of stem cell therapy is in the field of tissue engineering. Stem cells can be used to create new tissues and organs that can be transplanted into patients, which could potentially eliminate the need for organ donation and transplantation.[35] Despite the potential of stem cell therapy, there are still many challenges that need to be addressed. One of the main challenges is ensuring the safety and efficacy of stem cell therapies, as well as developing standardized protocols for their use.[36] Additionally, the high cost of stem cell therapy and the ethical concerns surrounding the use of ESCs continue to be major obstacles in the field.[37]

Stem cell transplantation is a promising therapy for various diseases and injuries. However, successful transplantation depends on several parameters that must be carefully considered. In this introduction, we will discuss the important factors that impact the success of stem cell transplantation. The first crucial parameter is the choice of stem cell type. Various types of stem cells, including ESCs, iPSCs, and ASCs, have been used in transplantation therapy. Each type of stem cell has unique properties, including differentiation potential and immunogenicity, which can impact the success of transplantation.[38] Another important parameter is the method of delivery. Stem cells can be delivered through various routes, such as intravenous injection, intra-arterial injection, and direct injection. The delivery method can impact the homing of stem cells to the target site, as well as their survival and engraftment.[39]

The timing of transplantation is also a critical parameter. The optimal time for stem cell transplantation can vary depending on the disease or injury being treated. For example, in acute injuries such as stroke or myocardial infarction, early transplantation may be beneficial, while in chronic diseases such as Parkinson’s disease, delayed transplantation may be more effective.[40] The immunological compatibility between the donor and recipient is another important parameter to consider. Immunological rejection can occur if the donor cells are not a close enough match to the recipient, which can limit the success of transplantation. Various methods, such as HLA matching and immunosuppression, can be used to minimize rejection.[41] Finally, imaging techniques can play a critical role in monitoring the success of transplantation. Non-invasive imaging techniques such as MRI and PET can be used to track the migration and survival of transplanted cells in vivo. This can provide important information about the distribution and function of the transplanted cells, which can help optimize transplantation parameters.[42]

One of the critical aspects of designing stem cells as a drug is the identification of the appropriate cell source. Various types of stem cells, including ESCs, iPSCs, and ASCs, have been investigated for their therapeutic potential. Each source has its advantages and disadvantages, and the selection of the cell source depends on the specific therapeutic application.[43] Another critical step in designing stem cells as a drug is genetic engineering. Genetic modification of stem cells can be used to enhance their therapeutic properties, such as their homing ability and immune evasion. For example, the overexpression of chemokine receptors on stem cells can enhance their homing to specific tissues, while the downregulation of immune-related genes can increase their immune evasion capacity.[44] Preclinical testing is also an essential step in the development of stem cells as a drug. This involves rigorous testing of the safety and efficacy of stem cells in animal models before they can be tested in humans. The preclinical testing also involves identifying potential risks and adverse effects of stem cell therapy.[45]

In conclusion, designing stem cells as a drug is a complex and challenging process that involves several steps, including cell sourcing, genetic engineering, and preclinical testing. The use of stem cells as a drug holds immense promise for the treatment of various diseases, and ongoing research in this field is expected to provide valuable insights into the development of safe and effective stem cell therapies.

Cite this article as: Yiğit S, Erbaş O. Designing Stem Cells As a Drug. JEB Med Sci 2024;5(1):159-163.

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

The authors received no financial support for the research and/or authorship of this article.

References

1. Yamanaka S. Induction of pluripotent stem cells from mouse fibroblasts by four transcription factors. Cell Prolif. 2008 Feb;41 Suppl 1:51-6.
2. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999 Apr 2;284:143-7.
3. Solmaz V, Tekatas A, Erdoğan MA, Erbaş O. Exenatide, a GLP-1 analog, has healing effects on LPS-induced autism model: Inflammation, oxidative stress, gliosis, cerebral GABA, and serotonin interactions. Int J Dev Neurosci. 2020 Nov;80:601-12.
4. Samanta P, Bhowmik A, Biswas S, Sarkar R, Ghosh R, Pakhira S, et al. Therapeutic Effectiveness of Anticancer Agents Targeting Different Signaling Molecules Involved in Asymmetric Division of Cancer Stem Cell. Stem Cell Rev Rep. 2023 Jul;19:1283-306.
5. Ding DC, Shyu WC, Lin SZ. Mesenchymal stem cells. Cell Transplant. 2011;20:5-14.
6. Friedenstein AJ, Deriglasova UF, Kulagina NN, Panasuk AF, Rudakowa SF, Luriá EA, et al. Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method. Exp Hematol. 1974;2:83-92.
7. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8:315-7
8. Alonso L, Fuchs E. Stem cells in the skin: waste not, Wnt not. Genes Dev. 2003 May 15;17:1189-200.
9. Martin GR. Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A. 1981 Dec;78:7634-8.
10. Alessandrini M, Preynat-Seauve O, De Bruin K, Pepper MS. Stem cell therapy for neurological disorders. S Afr Med J. 2019 Sep 10;109:70-7.
11. Oltulu F, Aktug H, Uysal A, Turgan N, Oktem G, Erbas O, et al. Immunoexpressions of embryonic and nonembryonic stem cell markers (Nanog, Thy-1, c-kit) and cellular connections (connexin 43 and occludin) on testicular tissue in thyrotoxicosis rat model. Hum Exp Toxicol. 2015 Jun;34:601-11.
12. Wobus AM, Wallukat G, Hescheler J. Pluripotent mouse embryonic stem cells are able to differentiate into cardiomyocytes expressing chronotropic responses to adrenergic and cholinergic agents and Ca2+ channel blockers. Differentiation. 1991 Dec;48:173-82.
13. Globerson Levin A, Rivière I, Eshhar Z, Sadelain M. CAR T cells: Building on the CD19 paradigm. Eur J Immunol. 2021 Sep;51:2151-63.
14. Gherghiceanu M, Popescu LM. Cardiomyocyte precursors and telocytes in epicardial stem cell niche: electron microscope images. J Cell Mol Med. 2010 Apr;14:871-7.
15. Fukasawa K, Lyu J, Kubo T, Tanaka Y, Suzuki A, Horie T, et al. MEK5-ERK5 Axis Promotes Self-renewal and Tumorigenicity of Glioma Stem Cells. Cancer Res Commun. 2023 Jan 30;3:148-59.
16. Papapetrou EP. Induced pluripotent stem cells, past and future. Science. 2016 Sep 2;353:991-2.
17. Zhu S, Rezvani M, Harbell J, Mattis AN, Wolfe AR, Benet LZ, Willenbring H, et al. Mouse liver repopulation with hepatocytes generated from human fibroblasts. Nature. 2014 Apr 3;508:93-7.
18. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007 Dec 21;318:1917-20.
19. Hockemeyer D, Jaenisch R. Induced Pluripotent Stem Cells Meet Genome Editing. Cell Stem Cell. 2016 May 5;18:573-86.
20. Qiu G, Zheng G, Ge M, Wang J, Huang R, Shu Q, Xu J. Functional proteins of mesenchymal stem cell-derived extracellular vesicles. Stem Cell Res Ther. 2019 Nov 28;10:359.
21. Trounson A, McDonald C. Stem Cell Therapies in Clinical Trials: Progress and Challenges. Cell Stem Cell. 2015 Jul 2;17:11-22.
22. Prigione A. Stem cell research moving forward. Stem Cell Res. 2021 Aug;55:102503.
23. King NM, Perrin J. Ethical issues in stem cell research and therapy. Stem Cell Res Ther. 2014 Jul 7;5:85.
24. Hilal T, Mountjoy LJ. Allogeneic Hematopoietic Stem Cell Transplant for Diffuse Large B-Cell Lymphoma: Evolving Role in the Era of CAR T-Cell Therapy. Curr Oncol Rep. 2023 Jun;25:599-607.
25. Kroon E, Martinson LA, Kadoya K, Bang AG, Kelly OG, Eliazer S, et al. Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat Biotechnol. 2008 Apr;26:443-52.
26. Ben Jehuda R, Shemer Y, Binah O. Genome Editing in Induced Pluripotent Stem Cells using CRISPR/Cas9. Stem Cell Rev Rep. 2018 Jun;14:323-36.
27. Michaeloudes C, Li X, Mak JCW, Bhavsar PK. Study of Mesenchymal Stem Cell-Mediated Mitochondrial Transfer in In Vitro Models of Oxidant-Mediated Airway Epithelial and Smooth Muscle Cell Injury. Methods Mol Biol. 2021;2269:93-105.
28. Baumann K. Achieving pluripotency. Nat Rev Mol Cell Biol. 2010 Oct;11:677.
29. Yuan X, Sun L, Jeske R, Nkosi D, York SB, Liu Y, et al. Engineering extracellular vesicles by three-dimensional dynamic culture of human mesenchymal stem cells. J Extracell Vesicles. 2022 Jun;11:e12235.
30. Lyerly AD, Faden RR. Embryonic stem cells. Willingness to donate frozen embryos for stem cell research. Science. 2007 Jul 6;317:46-7.
31. Ohnuki M, Takahashi K. Present and future challenges of induced pluripotent stem cells. Philos Trans R Soc Lond B Biol Sci. 2015 Oct 19;370:20140367.
32. Daley GQ. The promise and perils of stem cell therapeutics. Cell Stem Cell. 2012 Jun 14;10:740-9.
33. Lindvall O, Kokaia Z. Stem cells in human neurodegenerative disorders--time for clinical translation? J Clin Invest. 2010 Jan;120:29-40.
34. Fehlings MG, Wilson JR, Harrop JS, Kwon BK, Tetreault LA, Arnold PM, et al. Efficacy and Safety of Methylprednisolone Sodium Succinate in Acute Spinal Cord Injury: A Systematic Review. Global Spine J. 2017 Sep;7(3 Suppl):116S-37S.
35. Kawabori M, Shichinohe H, Kuroda S, Houkin K. Clinical Trials of Stem Cell Therapy for Cerebral Ischemic Stroke. Int J Mol Sci. 2020 Oct 6;21:7380.
36. Yalçın MB, Bora ES, Erdoğan MA, Çakır A, Erbaş O. The Effect of Adipose-Derived Mesenchymal Stem Cells on Peripheral Nerve Damage in a Rodent Model. J Clin Med. 2023 Oct 9;12:6411.
37. Lidz CW, Appelbaum PS, Grisso T, Renaud M 2004 Therapeutic misconception and the appreciation of risks in clinical trials. Soc Sci Med 58:1689–97
38. Trounson A, Thakar RG, Lomax G, Gibbons D. Clinical trials for stem cell therapies. BMC Med. 2011 May 10;9:52.
39. Hare JM, Traverse JH, Henry TD, Dib N, Strumpf RK, Schulman SP, Gerstenblith G, et al. A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. J Am Coll Cardiol. 2009 Dec 8;54:2277-86.
40. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009 Jun;119:1420-8.
41. Schram G, Pourrier M, Melnyk P, Nattel S. Differential distribution of cardiac ion channel expression as a basis for regional specialization in electrical function. Circ Res. 2002 May 17;90:939-50.
42. Nguyen PK, Lan F, Wang Y, Wu JC. Imaging: guiding the clinical translation of cardiac stem cell therapy. Circ Res. 2011 Sep 30;109:962-79.
43. Trounson A, McDonald C. Stem Cell Therapies in Clinical Trials: Progress and Challenges. Cell Stem Cell. 2015 Jul 2;17:11-22.
44. Drost J, Clevers H. Organoids in cancer research. Nat Rev Cancer. 2018 Jul;18:407-18.
45. Samsonraj RM, Raghunath M, Nurcombe V, Hui JH, van Wijnen AJ, Cool SM. Concise Review: Multifaceted Characterization of Human Mesenchymal Stem Cells for Use in Regenerative Medicine. Stem Cells Transl Med. 2017 Dec;6:2173-85.