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| EDITORIAL |
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| Year : 2022 | Volume
: 6
| Issue : 4 | Page : 199-200 |
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Development of stem cells in anesthesiology and intensive therapy
Zulkifli Zulkifli
Department of Anesthesiology and Intensive Care, Faculty of Medicine, Sriwijaya University/M. Hoesin Hospital, Palembang, Indonesia
| Date of Submission | 30-Apr-2022 |
| Date of Decision | 20-Jul-2022 |
| Date of Acceptance | 03-Aug-2022 |
| Date of Web Publication | 31-Oct-2022 |
Correspondence Address:
Zulkifli Zulkifli
Department of Anesthesiology and Intensive Care, Faculty of Medicine, Sriwijaya University/M. Hoesin Hospital, Palembang
Indonesia
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/bjoa.bjoa_127_22
How to cite this article:
Zulkifli Z. Development of stem cells in anesthesiology and intensive therapy. Bali J Anaesthesiol 2022;6:199-200 |
Stem cells have the potential to self-renew and can differentiate into cells of any creature. Stem cells may be found in both embryonic and adult cells. There are several levels of specialization. Because the developmental potential declines with each stage, unipotent stem cells cannot differentiate into as many cell types as pluripotent cells. Totipotent stem cells have the ability to divide and differentiate into cells from all species.[1],[2],[3],[4]
Mesenchymal stem cell (MSC)-mediated effects occur in the absence of MSC inclusion or grafting into the tissue (engraftment). According to fluorescence detection experiments, the half-life of cells after infusion is brief, with a population of less than 1% 1 week after infusion. In this environment, MSCs would function either directly by making contact with immune cells or indirectly by releasing paracrine substances, coordinating activities in processes such as tissue healing, neovascularization, apoptosis, phagocytosis, and immunomodulation.[5]
During embryogenesis, cells assemble into aggregations known as germ layers: endoderm, mesoderm, and ectoderm, which ultimately become differentiated cells and tissues of the fetus and, subsequently, the adult organism. Once human embryonic stem cells (hESCs) have differentiated into one of the germ layers, they become multipotent stem cells with solely the germ layer’s potential.[3],[6],[7]
This stage of human development is short. Following that, pluripotent stem cells exist as undifferentiated cells throughout the body, and their primary capacity is proliferation, which results in the synthesis of next-generation stem cells, and differentiation into specialized cells under particular physiological circumstances. External cues, such as physical contact between cells or chemical secretion by surrounding tissue, and internal signals, which are regulated by genes in DNA, might alter the process of stem cell specialization. In addition, stem cells serve as the body’s internal repair mechanism.[3],[6],[7]
MSCs are an interesting cell population. There is a large amount of research being carried out to translate MSC and related technologies so that they can be applied to various feasible therapies, for example, in the fields of nerves, heart, cartilage, liver, kidney, and others. The emergence of extracellular vesicles (EV) as a therapeutic modality has opened the door to drug-free regenerative medicine, with great utility. That is not to say that cell therapy will be surpassed by EVs, but EVs are a powerful offshoot of traditional cell therapy with the potential to reduce medication. However, clinical developments must always follow scientific understanding. We still have a lot to do to unravel the enigmatic MSC.[8]
Without incorporating or grafting MSCs into the tissue, MSC-mediated effects occur (engraftment). Fluorescence detection tests show that cells have a very short half-life upon infusion, with a population of less than 1% 1 week after infusion. In this scenario, MSCs will function directly by making contact with immune cells or other systems, or indirectly via the release of paracrine factors, coordinating processes such as tissue repair, neovascularization, apoptosis, phagocytosis, and immunomodulation.[5]
Two models of sepsis due to peritonitis have been used: (1) intraperitoneal injection of bacteria or bacterial components, such as lipopolysaccharide (LPS) and (2) cecal ligation and puncture (CLP) models. MSCs were administered by intravenous (IV) injection into the jugular vein or tail of mice. Injection of fibroblasts, saline, or MSCs that were not activated by heat shock was used as a placebo. Supportive treatment consisted of antibiotics and volume, which was administered to the experimental and placebo groups.[5],[9]
Mesenchymal could decrease plasma levels of pro-inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). There had been marked decrease of these cytokines in heart, lung, and kidney tissues. In contrast, increased plasma levels of IL-10 have been observed. Enhancement of this cytokine, which enhances immune tolerance by inhibiting Th1 and Th17 responses, is dependent on paracrine effects. MSCs, by releasing prostaglandin E2 (PGE2), reprogram the actions of host inflammatory macrophages, altering their phenotype and inducing IL-10 release.[5]
While suppressing the immune response may be detrimental in the setting of severe illness, infusion of MSCs promotes bacterial clearance, as measured by decreased bacterial CFU in the circulation, spleen, and lungs. Two MSC-secreted peptides with antibacterial activity have been discovered. The antimicrobial impact will be connected to the mechanism by which MSCs produce anti-apoptotic and pro-phagocytosis in neutrophils, monocytes, and macrophages. The paracrine factor FGF732 has been implicated in the suppression of innate immune system cell death.[5]
There are basically two types of models used. In animals, often mice, ventilator-induced lung injury (VILI) or orotracheal aspiration from bleomycin, lipopolysaccharide (LPS), or other endotoxins is induced. Other studies have used models of ex vivo perfused human lungs with immunological rejection or where lung injury has been induced by Escherichia coli or endotoxins. MSCs are infused IV or AO and the timing of administration varies.[5],[10] Local or systemic MSC infusion may generate immunomodulatory effects, reduce pulmonary edema, and restore the alveolar-endothelial barrier. Pro-inflammatory cytokines are consistently attenuated at systemic and pulmonary levels, and innate immunity promotes and improves the phagocytic activity of monocytes and macrophages, with the antimicrobial effects observed in sepsis.[5]
Animal studies have shown beneficial effects of MSC administration in acute respiratory distress syndrome (ARDS) models. However, preclinical testing of MSCs on the effects of SARS-CoV-2-induced ARDS cannot be performed during the current pandemic because it is time-consuming and involves high laboratory safety requirements. Administration of MSCs in the treatment of ARDS in humans has been reported in non-SARS-CoV-2 ARDS in the past in Phase 1 and Phase 2a safety trials.[9] Damages caused by gentamicin, cisplatin, and ischemia-reperfusion are the most widely used models. The IV route is the most common, although several studies have used the intraperitoneal route. The timing of MSC administration varied between studies (before injury and 2–24 h after induction of renal injury).[5]
The effect of MSCs showed an increase in the rate of proliferation of tubular epithelial cells and a decrease in their apoptosis. This underscores the role of MSC-mediated extracellular effects. Notably, in the ARDS model, two molecules with paracrine effects have been identified: (1) Lipocalin-2, which shows a stimulatory effect on proliferation, an inhibitory effect on apoptosis and induces increased expression of growth factors and anti-inflammatory factors, and (2) insulin-like growth factor-1 (IGF-1) which also shows a stimulatory effect on proximal tubular epithelial proliferation.[5]
MSCs initially were defined as cells that create the fibroblastoid colony-forming units (CFUs) that comprise the medullary stroma and are responsible for maintaining the hematopoietic microenvironment. These MSCs have been extensively used in anesthesiology especially in intensive care unit (ICU) settings to prevent septic shock, ARDS, and AKI throughout the patient’s stay in the ICU. Stem cells could potentially used as novel treatment in the future and regularly used for anesthesiologist.
Financial support and sponsorship
Not applicable.
Conflicts of interest
There are no conflicts of interest.
| References | |  |
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| 5. | Espinoza F, Aliaga F, Crawford PL. [Overview and perspectives of mesenchymal stem cell therapy in intensive care medicine]. Rev Med Chil 2016;144:222-31. |
| 6. | Larijani B, Esfahani EN, Amini P, Nikbin B, Alimoghaddam K, Amiri S, et al. Stem cell therapy in treatment of different diseases. Acta Med Iran 2012;50:79-96. |
| 7. | Sullivan S, Stacey GN, Akazawa C, Aoyama N, Baptista R, Bedford P, et al. Quality control guidelines for clinical-grade human induced pluripotent stem cell lines. Regen Med 2018;13:859-66. |
| 8. | Kuntin D, Genever P. Mesenchymal stem cells from biology to therapy. Emerg Top Life Sci 2021;5:539-48. |
| 9. | Deffune E, Prudenciatti A, Moroz A. Mesenchymal stem cell (MSC) secretome: A possible therapeutic strategy for intensive-care Covid-19 patients. Med Hypotheses 2020;142:109769. |
| 10. | Grippi MA, Elias JA, Fishman JA, Kotloff RM, Pack AL, Senior RM, et al. Fishman’s Pulmonary Disease and Disorders. 5th ed. New York: Elsevier Saunder; 2016. |
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