{"id":62406,"date":"2024-12-30T10:30:41","date_gmt":"2024-12-30T10:30:41","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=62406"},"modified":"2025-01-07T04:05:09","modified_gmt":"2025-01-07T04:05:09","slug":"stem-cell-therapies-approach-for-treating-cancers-opportunity-progress-and-challenges","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol17no4\/stem-cell-therapies-approach-for-treating-cancers-opportunity-progress-and-challenges\/","title":{"rendered":"Stem Cell Therapies approach for Treating Cancers: Opportunity Progress and Challenges"},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

Benchmark studies in stem cell research<\/strong><\/p>\n\n\n\n

1981 — From mice, embryonic stem cells were isolated<\/p>\n\n\n\n

1989 \u2013 The first knockout mouse was created. <\/p>\n\n\n\n

1998 \u2013 In an in vitro laboratory dish, stem cells from a human embryo are grown for the first time. <\/p>\n\n\n\n

2001 \u2013 Outside the body stem cells are used to make beating heart cells. <\/p>\n\n\n\n

2002 \u2013 Embryonic stem cells are shown to be capable of producing new heart muscle. <\/p>\n\n\n\n

2003 \u2013 Cardiac stem cells are discovered. <\/p>\n\n\n\n

2004 \u2013 Stem cells commit to a future of fat with one signal stem cells and progenitor cells reside in various tissues of the body and are capable of generating daughter cells of different lineages. Fat stem cells, in contrast, appear to be particularly well-suited for the job, as they are capable of transforming into fat, heart, bone, or muscle tissue. <\/p>\n\n\n\n

2007 \u2013 Discovered that human skin cells can be transformed to iPSCs quickly and efficiently. These iPSCs will be used to create new cardiac cells. <\/p>\n\n\n\n

2010-Thymosin beta-4, a protein, encourages stem cells to migrate to wounded tissue and assists in the growth of new blood vessels and muscle cells.<\/p>\n\n\n\n

2013- Identified compounds (polymers) that are derived from bacterial culture and can be used to repair damaged heart tissues in the body. <\/p>\n\n\n\n

2016 – An endless supply of clean blood for transfusion has been provided by stem cell-derived red blood cells. This could aid those who have lost blood as a result of surgery or an injury.<\/p>\n\n\n\n

2022 – Glyoxlase 1 as a therapeutic target in cancer and cancer stem cells<\/p>\n\n\n\n

2023 \u2013 ALPL-1 target for chimeric antigen receptor therapy in osteosarcoma. <\/p>\n\n\n\n

In\nboth industrialized and developing countries, cancer has the main cause of\nmortality1<\/sup>. Cancer is mainly treated using surgery, chemotherapy and\nradiotherapy, etc. Yet, therapeutic side effects, antibiotic resistance and\nmishit impact limits the adequacy of the treatment. Further metastatic cancers\nare not completely eradicated by traditional therapies. As a result, scientists\nhave attempting to discover novel and effective treatments which do not affect\nthe normal cells. And finally they discovered the stem cell therapy, which is\nsecure and efficient treatment2<\/sup>. Researchers are looking at using\nstem cells to rebuild the injured organs such as the heart, skin, bone, spinal\ncord, liver, pancreas and cornea, as well as to cure blood and rigid tissue\ncancer. They have two main properties: Renewing and differentiate into specific\ntypes of cells3<\/sup>.<\/p>\n\n\n\n

Stem\ncells are indistinct biological cells, which have the ability to develop into\nspecific forms of cells\/tissues and multiply (via mitosis) indefinitely.\nMulticellular creatures contain them. All the cells in our body are\ndifferentiated cells and only replicate a limited number of times and limited\nfunction. However, after development, somatic or adult stem cells are\nundifferentiated and found among differentiated cells throughout the body.\nThese cells are responsible for facilitating the healing, growth, and\nreplacement of cells that are lost each day4<\/sup>. At different times,\nstem cells can be discovered in different areas in the body. Stem cells are\npresent in every organ of our body; which has the ability to restore that\norgan. As we age, stem cells become less active and in some organs they are\ninactive for the majority of our lives. We may be able to heal or repair the\ndamage that is caused as a result of aging or disease; if we understand how to\nstimulate or reactivate stem cells that are unique to a tissue5<\/sup>.<\/p>\n\n\n\n

Somatic\nor adult stem cells are undifferentiated and found among differentiated cells\nin the whole body after development. The function of these cells is to enable\nthe healing, growth, and replacement of cells that are lost each day. In\ncollection of stem cells there are spare embryo \u2013 stem cells taken from embryos\nthat have been preserved at reproductive clinic lab; but have not yet been\nimplanted as well as special purpose embryo-an embryo generated by means of in\nvitro fertilization solely for the aim of obtaining stem cells followed that\ncloned embryo – an embryo that has been cloned in a laboratory utilizing the\nsomatic nucleus transfer procedure in addition Aborted fetus \u2013 stem cells from\nfetuses that were aborted during the early stages of development and also Adult\ntissue or organ-obtained by surgery6<\/sup>.<\/p>\n\n\n\n

According to scientists, stem cells can help to treat and understand the diseases better. They can be converting into a distinct of other types of cells because they had the ability to do so. They are employed for various purposes such as <\/p>\n\n\n\n

Restore damaged tissues or organs with fresh cells that grow in the lab. <\/p>\n\n\n\n

Reconstruct any malfunctioning organ parts.<\/p>\n\n\n\n

Look into the causes of cellular genetic anomalies.<\/p>\n\n\n\n

Look into the causes of diseases or the reasons why some cells develop into cancer cells.<\/p>\n\n\n\n

To assure the safety and effectiveness of new medications rigorous testing is done7-9<\/sup>.<\/p>\n\n\n\n

Stem cells are categorized as follows based on\ntheir potential differentiation: Totipotent cells can form all the cell types\nin a body that have evolved into all types of cells. The placenta along with\nthe merger of an egg and sperm cell (embryo) produces for further processes. It\nhas zygote formed at egg fertilization and pluripotent states that with the\nexception of placental tissue, the capability to modify into practically all\nforms. Ex: cells obtained from 3 germ layers. Whereas, the multipotent ability\nto modify into a varieties of unique cells belonging to a closely related cell\nfamily. These are generalized stem cells with the capacity to self-restoration\nand modify into specialized cells with specified function over a lengthy period\nof time ex: hematopoietic stem cells. Oligo-potent is the ability to divide\ninto a few varieties of cell kinds ex: lymphoid and myeloid stem cells. Finally\nthe Unipotent states that the ability to create only one cell type, but with\nthe capacity to self-renew, distinguishing stem cells from non-stem cells ex:\nmuscle stem cells, progenitor cells10<\/sup>.<\/p>\n\n\n\n

In general stem cells were classified into\nESC\u2019s (embryonic stem cells) and SSC\u2019s (somatic stem cells). SSCs are often\nreferred as adult stem cells, that are commonly multipotent also had the\ncapacity to modify into any type of cells with a specified origin. However,\nstem cell divided into the neural stem cells (NSCs), mesenchymal stem cells\n(MSCs), hematopoietic stem cells (HSCs), endothelial progenitor cells (EPCs)\nand so on11<\/sup>.<\/p>\n\n\n\n

Embryonic Stem Cells (ESCs) are pluripotent\nstem cells generated from blastocyst (inner cell mass), an embryo in its pre\nstages. After 4-5 days of fertilization, human embryos attain the stage of\nblastocyst, which contains 50-150 cells. The fertilized human embryo is\ndemolished when the embryo-blast (inner cell mass) is detached. They are\nharvested during in-vitro fertilization. They can renew themselves indefinitely\nand differentiate into almost all types of cells12<\/sup>. These ESCs\nprovide the wide range of therapeutic applications. Because of ethical\nconcerns, ESCs applications in research studies and human trails are\nrestricted. Instead induced pluripotent stem cells (iPSCs) are used13<\/sup>.<\/p>\n\n\n\n

Adult Stem Cells (ASCs) couldn\u2019t modify into many other cell types like ESCs. Adult tissues, organs, blood, cord blood and other tissues are used to isolate stem cells. Multipotent stem cells can be used in a various ways. After development they are located throughout the body multiplying by cell proliferation to renewal of died cells and heals injured tissues. They can renew themselves a number of times but not indefinitely. These are widely used because they are free of ethical issues.<\/p>\n\n\n\n

Literature Review<\/strong><\/p>\n\n\n\n

Neural stem cells (NSCs) <\/strong><\/p>\n\n\n\n

NSCs had been used to medicate brain, breast, prostate and lung malignancies because they can self-renew and develop into astrocytes, neurons or oligodendrocytes14-17.<\/sup><\/p>\n\n\n\n

Mesenchymal stem cells (MSCs)<\/strong><\/p>\n\n\n\n

MSCs are obtained from the bone marrow and can differentiate cartilage, bone, adipose tissue, stroma, muscle, connective tissue and tendon among other mesodermal cells. They are similar to NSCs in that they\u2019re easy to isolate and are commonly employed to treat cancer18-20<\/sup>.<\/p>\n\n\n\n

Hematopoietic stem cells (HSCs)<\/strong><\/p>\n\n\n\n

HSCs are utmost primordial blood cells,\ndevelop only in bone marrow and produce grown blood cells by the process of\ndifferentiation and proliferation. They produce billions of new blood cells\nevery day. They replace worn out and older blood cells in our body21-22<\/sup>.<\/p>\n\n\n\n

Induced Pluripotent Stem Cells (iPSCs) that\ncan be created from somatic cells are known as induced pluripotent stem cells.\nThese are altered form of adult stem cells. They had the capacity to modify\ninto a various forms of specialized cells throughout the body. Mechanism shows\nthat they have the ability to produce new cells for any condition of an organ\nor a piece of tissue. iPSCs are identical to ESCs, however they don\u2019t have the\nsame immune free and have no ethical concerns. As a result they may be more\nclinically useful than ESCs13<\/sup>.<\/p>\n\n\n\n

Umbilical cord stem cells states that the Cord\nblood is taken, stored and frozen at the time of delivery. Two types of stem\ncells are present in umbilical cord blood. They are: Haematopoietic stem cells\n(HSCs), Mesenchymal stem cells (MSCs). It can be used to cure blood diseases\nincluding sickle cell disease, thalassemia and leukaemia23<\/sup>.<\/p>\n\n\n\n

Amniotic fluid stem cell comes from Amniotic\nfluid which contains multipotent stem cells. Adipogenic, osteogenic, myogenic,\nendothelial, hepatic and also neuronal cell lines can all be differentiated\nfrom amniotic stem cells24<\/sup>.<\/p>\n\n\n\n

Fetal stem cells are found in the aborted\nfetal tissue. They had a limited ability for self-restoration. Normal tissue\nformation from these cells is more challenging. Properties of stem cells are\nthey have the capacity to proliferate and self-restore themselves for a long\ntime; they are generalized; they can modify into specific cell types in\nresponse to internal and external stimuli4, 5<\/sup>. Stem cell therapy is\nthe application of healthy adult stem cells to cure diseases or injury in\ntissue that has been healed or damaged. It has the capacity to self-renovate\nand modify into specific types of cells. This will potentially replace the\ndiseased and damaged body parts with little risk of rejection or negative\nconsequences. Healthy stem cells are needed to live. During cancer treatments\nhealthy stem cells are destroyed. So stem cell transplantation is the best\nmedication option. There are various stem cell therapies available, however the\nmost are still in the experimental stage, are expensive or are contentious25,\n26<\/sup>.<\/p>\n\n\n\n

There are three type of stem cells sources such as bone marrow followed that the bloodstream (peripheral blood), and umbilical cord blood from newborn27<\/sup>.<\/p>\n\n\n\n

Stem Cells roles in Cancer Therapy<\/strong><\/p>\n\n\n\n

Pluripotent Stem Cells were cultured to form\nthe somatic cells. These stem cells have same as ESCs but also lack ethical\nconcerns. However, T cells and NK cells were the essential resources of iPSCs28-30<\/sup>\nand anticancer vaccines are made from these stem cells31, 32<\/sup>.<\/p>\n\n\n\n

Adult stem cells were developing into many\ntissue and organ cell types. HSCs, MSCs and NSCs are commonly used for cancer\ntreatment. All adult blood cells were formed in the body by HSCs and are seen\nin bone marrow. Until date, the FDA has only approved the use of HSCs obtained\nfrom cord blood to treatment of multiple myeloma, leukemia and other blood\nrelated diseases33<\/sup>. MSCs are found in a variety of tissues and\norgans as well as play an important role in healing of tissue and also\nregeneration. They can multiply quickly and produce a variety of specialized\ntypes of cells in a short time. Osteocytes, adipocytes and chondrocytes are\nexamples of cells that can be cultured in in\nvitro<\/em>. MSCs are biologically distinct from other forms of stem cells qualities\nand they\u2019ve been frequently used to complement or deliver therapeutic\nsubstances in the treatment of several forms of malignant cancers34, 35<\/sup>.\nNSCs are self-renewing cells that arise from central nervous system and had the\nability to create new neurons and glial cells. They had been thoroughly tested\nin mice models for the treatment of both primary and secondary breast, lung and\nprostate cancers36-38<\/sup>.<\/p>\n\n\n\n

Cancer stem cells were called as Normal stem cells or CSC precursor\/progenitor cells have epigenetic alterations. These are also known stem-like cells, immature progenitors of tumor cells or tumor initiating cells. CSCs can be identified in tumor tissues and play a crucial role in cancer proliferation, migration and renovation. As a result focusing on CSCs could be beneficial and provides a promising treatment for a variety of solid tumors39<\/sup>. Stem cells involve cancer cells have special properties are Karyotype is abnormal; Progeny with a wide range of phenotypes; Capacity to cause tumors; Self-renewal potential that is vast and endless; Within tumors, it\u2019s uncommon and unusual; Mitotic activity is less than other cancerous cells; Self-renewal and differentiation both are highly dysregulated40<\/sup>.<\/p>\n\n\n\n\n\n
\"\"<\/td>\n\n

Figure 1: schematic diagram of stem cells and cancer stem cells (CSCs)<\/strong><\/p>\n<\/p>\n

Click here to view Figure<\/a><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Left panel: normal stem cell proliferation and differentiation. Right panel: CSCs and tumorigenesis as well as implications of CSCs for cancer therapy. (Source: Wenjing J, Jianhua P, Yue Z, William C S C, Kunlin J. (2012). The implications of cancer stem cells for cancer therapy. International Journal of Molecular Sciences. 13(12):16636-57. Doi: 10.3390\/ijms131216636).<\/p>\n\n\n\n

Types of Stem Cell Transplant<\/strong><\/p>\n\n\n\n

Depending on the source of the stem cells,\nthe  stem cell transplant were classified\ninto, Bone marrow transplant; Peripheral blood stem cell transplant; Cord blood\ntransplant. They are also called as hematopoietic stem cell transplants.\nExtremely the high doses of chemotherapy, frequently in combination with\nradiation therapy, were used to destroy all the cancer cells in a normal cancer\nstem cell transplant. This therapy also destroys the stem cells in our bodies.\nMyeloablation or myeloablative therapy is the term used for this. Stem cells\nare then given (transplanted) to repair those that were destroyed before.\nIdentical to blood transfusion, backup stem cells are injected into a vein. The\nintention could be for the cells to become normal stem cells after entering the\nbone marrow. Engraftment is the procedure of grafting cells onto another\nperson’s body over time41, 42<\/sup>. <\/p>\n\n\n\n

Transplants are classified as follows:\nAutologous, auto means self. Here the patient has their own donor. Stem cells\nfor transplant are comes from the same person and transplant comes from the\nother person either a similar or dissimilar match43<\/sup>.<\/p>\n\n\n\n

Autologous Stem Cell Transplant<\/strong><\/p>\n\n\n\n

In some cases the patient is treated with\nradiation therapy or chemotherapy. Stem cells and our immune system are damaged\ndue to these types of treatments. As a result, before starting cancer treatment\ndoctors extract or harvest our stem cells from our peripheral blood or bone\nmarrow. And it is kept frozen. After the chemotherapy or radiation therapy, the\nstem cells are returned to our body like blood transfusion. This helps to\nrestore our body\u2019s immune system and helps to make blood cells and fight\nillness. This procedure is also known as auto transplantation or stem cell\nrescue. <\/p>\n\n\n\n

PRO\u2019S: it avoids the rejection of engrafted\ncells or graft by our body because they are our own stem cells.<\/p>\n\n\n\n

CON\u2019S: In some cases the graft can fail by\nthey do not reach the bone marrow and make blood cells; while harvesting stem\ncells from our body, cancer cells are also harvested along with them and which\nis inserted into our body after cancer treatment. This leads to the growth of\ncancer again; the immune system of our body remains the same before and after\nthe transplant. So cancer cells have the ability to evade our immune system\u2019s\nattack; this is used to cure leukemia, multiple myeloma and lymphoma. It also\nsometimes utilised to treat cancers like testicular cancer and neuroblastoma44<\/sup>.<\/p>\n\n\n\n

Tandem Transplant<\/strong><\/p>\n\n\n\n

Tandem transplant (double autologous) is that\nthe two autologous transplant are performed within a period of time and does\nnot exceeds more than six months. Some cancers require two doses of\nchemotherapy, each accompanied by a stem cell transplant. Here the recipient\nalso acts as a donor. This type of transplant shows good result in\nneuroblastoma and multiple myeloma. The outcomes of this transplant are higher\nthan that of single transplant. So, doctors don\u2019t agree to this transplant45,\n46<\/sup>.<\/p>\n\n\n\n

Allogenic Stem Cell Transplant<\/strong><\/p>\n\n\n\n

Allogenic stem cell transplant were the given\nstem cells through transplant. The stem cells are derived from a giver whose\ntissue form is similar to that of the recipient. Family member, sister or\nbrother is the best donor. If this isn\u2019t matched donor might be found in common\npeople. This transplant is also known as MUD (matched unrelated donor)\ntransplant. MUD transplant are more dangerous than using a family member as a\ndonor. This transplant procedure is same as the autologous transplant.<\/p>\n\n\n\n

PRO\u2019S: Donor stem cells develop its own immune\ncells, which will help to eradicate any cancer cells that sustain the\nchemotherapy or radiation therapy. The graft-versus cancer or graft versus\ntumor effect is a term used to describe this phenomenon; if necessary, donor\nwill be asked or requested to contribute extra stem cells or even more white\nblood cells. Because they are free of cancer cells.<\/p>\n\n\n\n

CON\u2019S: The transplant, or graft, will fail if\nthe stem cells of donor die or removed by the body of patient or receiver\nbefore settles in the bone marrow; Another concern is that the immune cells of\nthe giver will not only kill the cancer cells, but also other healthy and\nnormal cells in the patient body. The medical term for this condition is\ngraft-versus-host disease; also a minor chance of despite the fact that donors\nare checked before they are used, certain illnesses from the donor cells are\ndonated into the recipient body; Infections that you’ve had before and that\nyour immune system hasn’t recovered from put you at a higher risk. The immune\nsystem has been brought under control. Following an allogeneic transplant,\nthese infections may resurface. Because drugs called immune suppressants keep\nyour immune system in check (suppress it). Infections of this nature can be\nfatal47-50<\/sup>.<\/p>\n\n\n\n

Syngenic Stem Cell Transplant:<\/strong><\/p>\n\n\n\n

Syngenic stem cell transplant is a unique form\nof transplant reserved for patients who have identical siblings (twins or\ntriplets). PRO\u2019S: Graft versus host disease does not occur; the implanted stem\ncells do not contain any cancer cells. CON\u2019S: The immune system of the donor\nand recipient are identical, there is no graft versus cancer impact. To prevent\ncancer from returning after the transplant, every effort should be made to kill\nall cancer cells51<\/sup>.<\/p>\n\n\n\n

Half Matched Stem Cell Transplant:<\/strong><\/p>\n\n\n\n

Half matched stem cell transplant is the utilization of family members as donors has improved in recent years. This form of transplant is utilized for patients who do not have a completely matched or identical family member. And this is called as half matched (haplo identical) transplant. This is an additional option for MUD transplant52<\/sup>. Demerits that occur after the stem cell transplant are Fever or chills; Shortness of breath; A feeling of heaviness in the chest; Blood pressure becomes low; Coughing; Chest discomfort; Urine is reduced; Faint and feels sick 53<\/sup>.<\/p>\n\n\n\n

Stem Cell Resutation in Cancer Therapy<\/strong><\/p>\n\n\n\n

Multiple techniques can be used to modify stem\ncells, most notably NSCs and MSCs for use in cancer therapy. The following are\nexamples of common modifications: Enzyme \/ prodrug therapy: NSCs and MSCs can\nbe genetically engineered to produce enzymes which transform non-toxic prodrugs\ninto cytotoxic drugs. When transformed stem cells are implanted into\ntumour-bearing mice, the foreign enzyme transforms prodrug into a deadly\ncompound, causing the tumor cells to die. From this we conclude that, release\nof drug can be controlled in terms of quantity, timing, and location. Suicide\ngene therapy, also termed as enzyme\/prodrug therapy, was the first designed NSC\ntherapeutic use to reach clinical trials54,55<\/sup>. The enzyme cytosine\ndeaminase (CD) is a common enzyme utilized in enzyme\/prodrug treatment. The\nprodrug 5-fluorocytosine (5-FC) is converted to the harmful Variant\n5-fluorouracil by CD. Glioblastoma (GBM) cell development was suppressed by a\npair of CD-bearing mouse NSCs and 5-FC. 5-FC injection of CD-expressing MSCs\ninto the brain Tumor development was also slowed in Human HB156<\/sup>. F3\ncells are modified to exhibit CD (HB1.F3.CD) in one of the most often utilized\ncytotoxic therapies57<\/sup>. HB1.F3.CD\/5-FC therapy was currently used in\nthe first human therapeutic trial (ClinicalTrials.gov identifier: NCT01172964),\nin which patients received oral 5-FC and HB1.F3. CD cells have been implanted\ninto the cavity wall succeeding GBM abscission. <\/p>\n\n\n\n

The research has been finished, but the\nresults have not yet been made public. In October 2018, a new trial utilizing\nengineered NSCs to cure glioma (ClinicalTrials.gov identifier: NCT02015819)\nwill be finished. Suicide gene therapy has also used the herpes simplex\nvirus-thymidine kinase (HSV-TK)58<\/sup>. HSVTK phosphorylates the\nmonophosphorylate Ganciclovir (GCV), a prodrug, to create cytotoxic\ntriphosphate ganciclovir (GCV-TP). During cell division, GCV-TP integrates into\nthe DNA of surrounding cells, causing cell death by inhibiting DNA polymerase.\nThe intra-tumoral HSV-TK-transduced NSC (NSC-TK) injection succeeded by\nintraperitoneal GCV injection daily for 10 days (two 15 mg\/kg doses\/day)\nefficiently cured C6 gliomas in rats. Six of nine rats survived 100 days after\nbeing injected with no evidence of tumor. NSCs-TK inserted into the brain moved\nto the contra lateral hemisphere, co-localized with U87 cells, and provided\nprolonged viability on GCV-treated animals, according to another study59,\n60<\/sup>.<\/p>\n\n\n\n

Secreted Agents<\/strong><\/p>\n\n\n\n

Stem cells are able to behave as in situ drug industries, secrets anti-cancer drugs for long periods of time and overpower some of the constraints of cancer therapy, such as raised systemic virulence and low drug half-life. TNF-related apoptosis-inducing ligand (TRAIL) is a frequently utilized secreted therapeutic drug that promotes apoptosis in tumor cells61<\/sup>. In vivo<\/em>, however, its short half-life decreases its therapeutic efficacy. Encapsulating TRAIL-expressing stem cells in a synthetic extracellular matrix (sECM) which is injected into the GBM resection cavity following surgical debulking should help to attenuate this. At the resection margins, the encapsulated cells might continuously release therapeutic chemicals. In mice, this method reduces the redevelopment of metastatic and intrusive brain tumors and improves survival62<\/sup>.<\/p>\n\n\n\n

Table 1: Methods of strategies on Cancer and Application in stem cell research<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Strategies<\/strong><\/p>\n<\/td>\n

\n

Cancer Types<\/strong><\/p>\n<\/td>\n

\n

Stem Cell Applications<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Stem cell\u00a0<\/p>\n

modifications<\/p>\n<\/td>\n

\n

Glioma<\/p>\n<\/td>\n

\n

MSCs (lentiviral and retroviral transduction with S-TRAIL and HSV-TK)18-20<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

Enzyme\/prodrug<\/p>\n

\u00a0therapy<\/p>\n<\/td>\n

\n

Colon Adenocarcinoma<\/p>\n

Metastatic lung cancer Primary lung cancer<\/p>\n

Glioma<\/p>\n<\/td>\n

\n

NSCs (retroviral transduction with CD)33<\/sup><\/p>\n

NSCs (baculoviral transduction with HSV-TK)58<\/sup><\/p>\n

MSCs (retroviral transduction with CD )34-35<\/sup><\/p>\n

NSCs (adenovirus transduction with a rabbit CE)65<\/sup><\/p>\n

NSCs (manipulated to express CE)14-17<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

Secreted agents<\/p>\n<\/td>\n

\n

Breast cancer brain\u00a0 Metastases<\/p>\n

Breast cancer<\/p>\n

Glioma<\/p>\n<\/td>\n

\n

NSCs (retrovirus transduction with IL-4 )58<\/sup><\/p>\n

NSCs (adenovirus transduction with TRAIL)59<\/sup><\/p>\n

NSCs (encapsulated in sECM after being modified to express S-TRAIL)60<\/sup><\/p>\n

NSCs (lentivirus transduction with antiHER2Ab)15<\/sup><\/p>\n

\u00a0<\/p>\n<\/td>\n<\/tr>\n

\n

Viral therapy<\/p>\n<\/td>\n

\n

Hepatocellular carcinoma<\/p>\n

Solid tumor<\/p>\n

Glioma<\/p>\n<\/td>\n

\n

\u00a0\u00a0\u00a0\u00a0\u00a0 MSCs (modified to over express IFN-beta)51<\/sup><\/p>\n

\u00a0\u00a0\u00a0\u00a0\u00a0 NSCs (affected with CRAd-S-pk7)63<\/sup><\/p>\n

\u00a0\u00a0\u00a0\u00a0\u00a0 MSCs (armed with oHSV)64<\/sup><\/p>\n

\u00a0\u00a0\u00a0\u00a0\u00a0 MSCs (affected with measles virus)65<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

Nanoparticle carriers<\/p>\n<\/td>\n

\n

Hematologic malignancies<\/p>\n

Liver disease<\/p>\n

Solid tumor<\/p>\n<\/td>\n

\n

NSCs (armed with gold nanorods) 68-70<\/sup><\/p>\n

MSCs (armed with poly-lactic acid nanoparticles and lipid nanocapsules)69-70<\/p>\n<\/td>\n<\/tr>\n

\n

Regenerative medicine<\/p>\n<\/td>\n

\n

Lymphomas<\/p>\n

Hematologic malignancies<\/p>\n<\/td>\n

\n

MSCs (armed with nanoparticles)71<\/p>\n

HSCs (allogeneic transplantation)72-73<\/p>\n<\/td>\n<\/tr>\n

\n

Immunotherapy<\/p>\n<\/td>\n

\n

Liver disease<\/p>\n

Solid tumor<\/p>\n

Lymphomas<\/p>\n

Melanoma<\/p>\n

Glioma<\/p>\n<\/td>\n

\n

iPSCs (engraftment of patient-specific iPSCs)74-75<\/p>\n

HSCs (trigger of graft vs. tumor effect )76-77<\/p>\n

HSCs (allogeneic transplantation)78-79<\/p>\n

iPSCs (produce T cells)80-81<\/p>\n

HSCs (genetically modified HSCs to produce antigen-specific CD8 T cells)82-83<\/p>\n<\/td>\n<\/tr>\n

\n

Targeting CSCs<\/p>\n<\/td>\n

\n

Glioma<\/p>\n<\/td>\n

\n

HSCs (engineering the proteome profile of HSCs )84<\/sup><\/p>\n<\/td>\n<\/tr>\n

\n

Anticancer drug screening<\/p>\n<\/td>\n

\n

\u00a0<\/p>\n

Glioma<\/p>\n

\u00a0<\/p>\n<\/td>\n

\n

Cancer tissue-derived iPSCs (allocate cellular targets)85<\/sup><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Viral Therapy<\/strong><\/p>\n\n\n\n

Unlike standard attenuated viruses, oncolytic viruses (OVs) conditionally reproduce in cancer cells. OVs has proliferated throughout the body and are able to conceal from the immune system. NSCs that have been infected with OVs can still home to cancer cells, and OVs supplied via NSCs had stronger anticancer effects in vivo<\/em> than the viruses alone against GBMs63<\/sup>. Similarly, NSC-delivered OVs improved viability in glioma-bearing mice after radiation and temozolomide treatment64. Former medical trial for adenovirus-based anti-glioma gene therapy indicated adequate tolerability and no significant side effects65<\/sup>. MSC-mediated virus delivery is also an optimistic method for cancer therapy. The study revealed that the combination of attenuated measles virus’s powerful oncolytic activity and MSCs’ unique immune privileged and tumor tropic features could combat hepato-cellular cancer66<\/sup>. MSCs infected with the measles virus were supplied systemically to tumor injected ortho-topically in the liver, where they transported MV infectivity to cancer cells via hetero-fusion and inhibited tumor development. MSC-mediated administration of oncolytic Herpes simplex virus (oHSV) in a GBM resection mice model increased the virus’ anticancer impacts. oHSV generated by MSC dynamically infected GBM cells in this method, destroying cancer cells in vitro<\/em> and in vivo<\/em>. Combining oHSV with TRAIL might be useful in preventing tumor resistance. In mice with oHSV- and TRAIL-resistant GBMs, oHSV\/TRAIL-loaded MSCs successfully triggered cancer cell death and increased median viable time67<\/sup>.<\/p>\n\n\n\n

Nanoparticle carriers<\/strong><\/p>\n\n\n\n

Nanoparticle carriers (NPs) are used in delivery systems to preserve high-concentration insoluble chemotherapeutic chemicals from decay in a hostile biotic habitat. The use of stem cells as NP delivery agents can overcome constraints such as failed to focus micrometastatic abrasion, ineffective distribution in solid tumors, and others. Stem cells can also protect therapeutic molecules from host immune-surveillance by reducing the uncontrolled absorption of nanoparticles by mononuclear cells68,69<\/sup>. MSCs effectively absorbed NPs and can operate as NP delivery agent in brain malignancies. For tumor-tropic therapy, MSC cell membranes could be armed with doxorubicin-containing porous silica nanorattles70<\/sup>. Compared to free drug or drug delivery systems by silica nano-rattles alone, our technique boosted and extended intra-tumoral drug distribution and accelerated tumor cell death. As a result, stem cell-mediated NP-based medication delivery holds a lot of promise for cancer treatments and deserves more research71<\/sup>.<\/p>\n\n\n\n

Other Applications of Stem Cells in Cancer Therapy<\/strong><\/p>\n\n\n\n

Regenerative medicine: Stem cells can be employed to heal human tissues following chemotherapy betwixt of their self-restoration and modification capacities. Later medication of cancers along with elevated-dose radiation or chemotherapy, HSC transplantation has been frequently used in clinical trials to aid long-term haematological recovery. This treatment acts by delivering stem cells which specialize into a required kind of blood cell in order to restore bone marrow in marrow malfunction disorders (e.g., aplastic anemia) and to cure blood cell related genetic diseases. Only one HSC can restore hematopoiesis in patients after transplantation and effective engraftment72,73<\/sup>. Healthy iPSCs produced from patient tissues might hypothetically be utilised to renew tissues which had been injured by tumors or treatment. iPSCs can be used to create different tissues in regenerative medicine. Cancer patients’ iPSCs may benefit from iPSC therapy to repair or replace those that have been destroyed by chemotherapy, radiation, or surgery. In vivo<\/em> engraftment of iPSC-derived tissues is required for regenerative treatment mediated by human iPSCs. Merely a certain types of human iPSC-derived cells (for example, hepatocytes) had been effectively implanted in animal models to yet74,75<\/sup>.<\/p>\n\n\n\n

Immunotherapy<\/strong><\/p>\n\n\n\n

Some hematological malignancies may be cured solely by an immune-mediated anticancer response succeeding allogeneic HSC transplantation76,77<\/sup>. HSCs are promising for use in Cancer immunotherapy because they can be genetically modified to produce chimeric antigen receptors (CARs) or T-cell receptors (TCRs) which target tumor-associated antigens78,79<\/sup>. Immunotherapy techniques could also benefit from patient-specific iPSCs80, 81<\/sup>. T lymphocyte-derived human iPSCs contain the pre-rearranged TCR gene that can be additionally stimulated to develop into functioning active T cells. By reorganizing chosen T cells to become iPSCs and then develop again into T lymphocytes for insertion into victims, functional, tumor antigen-specific T lymphocytes could be created in vitro. The safety of T cell-derived human iPSCs is required to be confirmed82,83<\/sup>.<\/p>\n\n\n\n

Targeting CSCs<\/strong><\/p>\n\n\n\n

CSCs are multipotent, self-renewing, and multiplicative, allowing tumor invasion and metastasis to occur quickly. CSCs must therefore be targeted appropriate to achieve increased treatment efficacies and avoid tumor reoccurrence. Normal stem cells could be utilized to target CSCs in cancer therapy since CSCs can attract them. Normal stem cell interactions with CSCs minimize inflammation and death while suppressing tumor proliferation, angiogenesis, and metastasis. It has compared the capability of NSCs and HSCs in anti-glioblastoma therapy84<\/sup>, concluding that HSCs are more suited for creating techniques to control glioblastoma CSC activities than NSCs because HSCs are rarely exposed to neoplastic conversion in neural tumors than NSCs. In the same way, modified HSCs may make it easier to create cell systems that can be used in a variety of applications. Engineered HSCs may also make it easier to create cell systems that can trigger targeted CSC death.<\/p>\n\n\n\n

Anticancer drug screening<\/strong><\/p>\n\n\n\n

iPSCs could be utilized to monitor potential antitumor medicines as well as treat malignancies directly. Patient cancer tissue-derived iPSCs can be differentiated to produce cell forms which are further biologically similar to human tumor than currently accessible drug scanning ideas, such as classical cancer cell lines, mice xenograft models, and mouse tumors. Hepatotoxicity may also suppress numerous potential antitumor medicines out from arriving the health care, and also it might be tested by using hepatocytes obtained out of human iPSCs of varied genetic backgrounds85<\/sup>.<\/p>\n\n\n\n

Innovation of Stem Cell Research<\/strong><\/p>\n\n\n\n

Molecule with little toxicity reduces the effects of cancer cells<\/strong><\/p>\n\n\n\n

SVC 112 (SuviCa, Inc.), a compound firmed on the chemical bouvardin, was discovered to be effective against neck and head cancer stem cells by researchers86<\/sup>. They came to the conclusion that the cancer stem cells operate as tumour growth controllers, and disrupting this group of cells will cause the cancer to slow or cease87<\/sup>.<\/p>\n\n\n\n

Inhibiting Progeny Stem Cells<\/strong><\/p>\n\n\n\n

To treat stomach malignancies, researchers are\nusing osteopontin inhibitors and CD44+<\/sup> antibodies to see if they can\nlimit the growth of Lgr5-CD44+<\/sup> cells88<\/sup>.<\/p>\n\n\n\n

A Protein Vital for Leukemic Stem Cell function is Identified<\/strong><\/p>\n\n\n\n

The protein HBO1 is needed for leukemic stem cell survival. HBO1 is a protein that aids in the high expression of critical genes that assist leukemic stem cells maintain their functional features89<\/sup>.<\/p>\n\n\n\n

Targeting Cancer Stem Cell Energy Supply<\/strong><\/p>\n\n\n\n

Even if only a few survive chemotherapy, tumors can recur if cancer stem cells are not present. As a result, by inhibiting the glutamine satisfy and forcefully starve the tumor, targeting CD9 could provide a treatment option for the disease90-92<\/sup>.<\/p>\n\n\n\n

Biomarker and Drug Target for Cancer Stem Cells<\/strong><\/p>\n\n\n\n

Plectin could become a more common\npharmacological target than the ones already available. Plectin has the\npotential to be both a drug lead and a drug delivery agent. Plectin is mostly\nexpressed intracellularly, however it is connected to tumor invasion and\nmetastasis when it is translocated to the cell surface93.<\/p>\n\n\n\n

Conclusion<\/strong><\/p>\n\n\n\n

Stem cell therapy is only hope for cancer treatment. It may open new doors for the cancer treatment. Not only stem cell therapy be used to treat cancer but it can also be used to treat a variety of other diseases also. In this thesis, we focus on the stem cell, its types, cancer stem cells, stem cell therapy, stem cell modifications and provide update on the other applications of stem cells in cancer therapy. Different types of stem cells are used in anti-cancer therapy depending on their inherent capabilities. Despite the fact that clinical trials were successful, there are still many obstacles to overcome. Outcomes of stem cell therapy in cancer are highly encouraging but still it needs to enhance the treatment\u2019s safety and efficacy.<\/p>\n\n\n\n

Acknowledgement <\/strong><\/p>\n\n\n\n

The\nauthors would like to extend their sincere appreciation to the Research and\nDevelopment Cell (RDC) at PRIST Deemed University for their support during\nProject works.<\/p>\n\n\n\n

Funding Sources<\/strong><\/p>\n\n\n\n

The\nauthor(s) received no financial support for the research, authorship, and\/or\npublication of this article<\/p>\n\n\n\n

Conflict of Interests <\/strong><\/p>\n\n\n\n

The\nauthors do not have any conflict of interest<\/p>\n\n\n\n

Data Availability\nStatement<\/strong><\/p>\n\n\n\n

This\nstatement does not apply to this article<\/p>\n\n\n\n

Ethics Statement<\/strong><\/p>\n\n\n\n

This\nresearch did not involve human participants, animal subjects, or any material\nthat requires ethical approval<\/p>\n\n\n\n

Informed Consent\nStatement<\/strong><\/p>\n\n\n\n

This\nstudy did not involve human participants, and therefore, informed consent was\nnot required<\/p>\n\n\n\n

Permission to reproduce material from other\nsources<\/strong><\/p>\n\n\n\n

Figure.1\nschematic diagram of stem cells and cancer stem cells (CSCs)<\/p>\n\n\n\n

Wenjing J, Jianhua P, Yue Z, William C S C,\nKunlin J. (2012). The implications of cancer stem cells for cancer therapy.\nInternational Journal of Molecular Sciences. 13(12):16636-57. Doi:\n10.3390\/ijms131216636).<\/p>\n\n\n\n

Authors\u2019 Contribution<\/strong><\/p>\n\n\n\n

Bakrudeen Ali Ahmed Abdul \u2013 Conceptualization, Writing \u2013 Supervision. <\/p>\n\n\n\n

Vijay Lobo \u2013 First author, Data Collection, Draft, Writing, <\/p>\n\n\n\n

Shenbagavarshini Sivasankar \u2013 Visualization, Data typing, writing part. <\/p>\n\n\n\n

Abdul Hakeem K \u2013 Resources, Editing, Rewriting , Data collection<\/p>\n\n\n\n

Mahmood Pasha \u2013 Editing, Writing, Resources, Table, References<\/p>\n\n\n\n

Arun Kumar R\u2013 Rewriting, Co-supervision, Editing, Data collection<\/p>\n\n\n\n

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