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Layout table for location contacts Contact: Federico Simon Simon. FedericoRey mayo. Andreas mayo. More Information. Stem cell mesenchymal stem cell mesenchymal stromal cell diabetes mellitus diabetic nephropathy diabetic kidney disease kidney GFR.
National Library of Medicine U. National Institutes of Health U. Department of Health and Human Services. The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Phase 1. In addition, MSCs were isolated virtually from any type of tissues, including the bone marrow stroma, adipose tissue, and umbilical cord blood.
It has been hypothesized that MSCs contribute to tissue repair by differentiating into organ-specific cells and replacement of damaged tissues.
MSCs secrete a variety of molecules including cytokines, growth factors, anti-oxidants and pro-angiogenic factors, and those that stimulate cell proliferation and angiogenesis, decrease the response to stress and apoptosis of damaged cells, and regulate the local and systemic inflammatory and immune response, thus contributing to tissue repair [ 24 , 25 ]. The application of MSCs in treating kidney diseases is widely studied and is superior to the application of other SCs.
Progenitor cells exhibit differentiation potential between SCs and mature cells and were found in many organs, including the bone marrow [ 26 ], gastrointestinal mucosa [ 27 ], liver, brain, prostate, and skin. These cells play a part in maintaining the wounding process to replace the damaged or dead cells, participating in the normal cell turnover of organs.
With inherent renal differentiation potential and the potential for autologous treatments, RSPCs were considered to be ideal sources of cell therapy for treating kidney diseases. ESCs that are characterized by features of self-renewability and multilineage differentiation hold great promise in cell therapy and kidney regeneration.
Numerous studies have shown that mouse embryonic stem cells mESCs can integrate into kidney compartments, suggesting a possible efficacy for kidney repair. In addition, the exposure of ESCs to factors required for renal specification, such as retinoic acid, activin A, and bone morphogenic proteins BMPs , induces differentiation of these cells into renal lineage cells in vitro [ 33 , 34 , 35 ].
Geng et al. Similarly, mESC implantation in mice with renal failure induction RFI employing cisplatin significantly decreased the mortality, avoiding a greater histological deterioration related to the disease. Glomerulosclerosis or collapsed glomeruli were not observed in RFI mice treated with mESCs; even some regeneration data were found characterized by large nuclei with prominent [ 37 ].
Mata-Miranda et al. Patients require renal replacement therapy when their kidney disease progresses to ESRD. Although dialysis offers a temporary solution for patients, it has several limitations. Dialysis does not address the loss of hemostatic and endocrine function of the kidney and its associated complications [ 5 ]. Kidney transplantation remains to be the best curative treatment strategy to restore total kidney function, but the demand for organs suitable for transplantation has reached a level that far outstrips the static supply [ 39 ].
Due to the precise nature of renal structure, which comprises several kinds of cells and with complex anatomy, the kidney has become the most difficult organs of reconstruction. Many protocols have induced the differentiation of ESCs to generate complex structures resembling kidneys, termed organoids, which contain multiple renal cell types and are capable of self-organization. Morizane et al. Takasato and colleagues have generated kidney organoids that contain not only nephrons and collecting duct but also renal interstitium and an endothelial network.
The proximal tubules of these show functional maturity to some extent [ 41 ]. The ESC-derived kidney progenitors implanted into immunocompromised mice generated perfused glomeruli containing human capillaries, podocytes with regions of mature basement membrane, and mesangial cells. The vascularized glomeruli showed the ability to produce ultrafiltrate that is processed by adjacent tubules [ 42 ]. The latest research is consistent with previous ones. By inducing the directional differentiation of ESCs into ureteric bud progenitor cells and co-culturing with dissociated primary metanephric mesenchyme pMM , the organoids composed of nephron structures and collecting ducts could be produced, which displayed the presence of endothelial cells forming a vascular network [ 43 ].
Although scientists thought they have found a strategy to isolate hESCs from single blastomeres without destroying the embryos, legal and ethical controversies still limit the research and applications of ESCs [ 44 ].
Another concern about this technique is that cells and tissues derived from ESCs are at high risk of degenerating into neoplasms, especially teratomas. Yamamoto et al.
What is more, ESC-derived differentiated cells are allogenic in nature and inevitably suffer from all the issues related to allografts and immunocompatibility, such as acute and chronic rejection, and graft versus host disease. Induced pluripotent stem cells sharing many of the regenerative properties of ESCs are considered effective alternative cell sources for ESCs. Indeed, iPSCs could retain both genetic background and peculiar epigenetic memory of the cells of origin, providing indisputable advantages in cell therapy, kidney regeneration, and other biomedical applications.
To date, the human iPSCs have been generated from multiple sources, including skin fibroblasts, keratinocytes [ 46 , 47 ], extraembryonic tissues [ 48 ], cord blood [ 49 ], peripheral blood cells [ 50 ], hepatocytes, stomach cells [ 51 ], dental pulp cells [ 52 ], and even fully differentiated lymphocytes such as T and B cells [ 53 ]. Interestingly, the terminally differentiated kidney cells are reprogrammed to pluripotency. Song et al. The kidney-derived iPSCs resemble that of human embryonic stem cell-like colonies in morphology and gene expression.
Considering their potential risks as oncogenes Klf4 and c-Myc, Montserrat et al. Moreover, generation of iPSCs from exfoliated renal tubular cells that are present in urine is regarded as a simple, non-invasive method for obtaining iPSCs [ 56 , 57 , 58 ]. Induced pluripotent stem cells are considered as an effective means to alleviate renal tissue damaged in AKI and CKD, and paracrine pathways may be the major mechanism.
The administration of iPSC-derived conditioned medium attenuated AKI by downregulating the oxidative stress response in ischemia-reperfusion rats [ 59 ].
The recent result from Collino et al. In the study conducted by Lee et al. It is worth noting that high doses of iPSC accumulation might lead to renal dysfunction. In the same research, Lee et al. When carrying out cell therapy for treatment of AKI using iPSCs, the cell dose for transplantation and the monitoring of renal blood perfusion should be taken care of [ 61 ].
For the efficacy of iPSC therapy in chronic kidney disease, Caldas et al. It was shown that both treatments improved function and structure of the kidney. In particularly, proteinuria was reduced only in the iPSC group. The pluripotency of PSCs raises concerns on high risk of maldifferentiation of the cells and even tumor formation, when these cells are administered without pre-differentiation.
An attractive alternative consists in the derivation of renal progenitors from iPSCs, which could be achieved by the controlled activation of the correct network of nephric transcription factors. The injected iPSC-derived renal progenitor cells robustly engrafted into damaged tubuli and restored renal function and structure in cisplatin mice with AKI [ 63 ].
Similarly, iPSC-derived MSC therapy effectively protected the rat kidney from acute ischemia-reperfusion injury [ 64 ]. All the studies above demonstrate that iPSCs are a valuable source of engraftable cells with regenerative activity for kidney disease and create the basis for future applications in stem cell-based therapy [ 66 ].
Induced pluripotent stem cells are regarded as the best source for producing new kidney tissues for transplantation, which are potentially derived from patients and used as a renal replacement therapy without immunosuppression. Although it is difficult to regenerate the entire kidney in vitro, recent advances in the field of SCs have enabled in vitro generation of organoids [ 67 , 68 , 69 , 70 , 71 , 72 , 73 ].
The kidney organoid formation involves stimulation of a stepwise differentiation process, in which movement occurs from monolayered iPSCs to primitive streak then intermediate mesoderm to kidney lineage cells [ 40 , 69 , 70 , 71 , 74 ].
Several protocols for differentiation of PSCs to kidney cell fates have been established to date. In the early days, several studies have reported successful differentiation of human pluripotent stem cells hPSCs into either ureteric epithelium [ 35 , 73 , 75 ] or metanephric mesenchyme [ 35 , 72 , 76 ] in vitro. Takasato et al. The kidney organoid reported is transcriptionally similar to that of fetal human kidneys and showed functional maturity, in which the proximal tubules within the organoids displayed megalin-mediated and cubilin-mediated endocytosis, and responded to a nephrotoxicant to undergo apoptosis [ 70 ].
Bioengineering represents one possible approach for generating the complex branching structures of the kidney. Scaffolds are temporary physical support obtained from a variety of biomaterials and help to accommodate cells and support their three-dimensional 3D growth during tissue developmental stage [ 77 ].
Scaffolds have become a hope for clinical translation due to their features of biocompatibility, biochemical and biological cues for cell adhesion, proliferation, migration, differentiation, and continued function [ 78 , 79 ]. Renal scaffolds were successfully produced from porcine, rat, and human kidneys [ 80 , 81 , 82 , 83 , 84 ].
Considering as a potent cell source for scaffold recellularization, embryonic stem cells and adipose tissue-derived stem cells have been seeded into renal scaffolds, achieving cell adherence, proliferation, differentiation, endothelialization, and vascularization [ 84 , 85 , 86 , 87 ]. Du et al. Ciampi et al. It has been reported that human whole kidney scaffold re-endothelialization can be done using hiPSC-ECs and fully perfused with human whole blood [ 84 ].
Microfluidic organ-on-a-chip technology has been used to construct an in vitro model of human kidney glomerulus. Musah et al. The hiPSC-derived podocytes were cultured on the top of the laminin-coated membrane and primary human glomerular endothelial cells on the opposite side of the same membrane to recapitulate the podocyte-GBM-endothelial interface.
The microfluidic glomerulus chip recapitulates some of the normal molecular filtration properties of the functional human kidney glomerular capillary wall and then replicates pharmacologically induced podocyte injury and albuminuria as seen in patients [ 90 , 91 ]. Although not yet clinically available for transplantation, hiPSC-derived kidney organoids provide dominant models for studying the pathophysiology of kidney diseases, through which we can better understand gene mutations and disease phenotypes of the disease, mimicking disease progression.
In addition, mouse models commonly used in previous studies could not fully recapitulate human genotypes and phenotypes [ 98 , 99 ]. For example, KAL-1 encodes a basement membrane protein called anosmin-1 that is present on the surface of ureteric bud UB. Another case is that the autosomal dominant polycystic kidney disease in humans often inherits heterozygous loss-of-function mutations in either PKD1 polycystic kidney disease-1 or PKD2 polycystic kidney disease-2 , while the mice displays only very mild cystic disease in the same situation [ , ].
Species-specific models developed by hiPSCs that carry naturally occurring human mutations are regarded as important complement to mouse models, showing a great promise in studying kidney development and disease process. For example, a family with adult-onset autosomal dominant focal segmental glomerulosclerosis FSGS was recently found to carry a new germline missense heterozygous mutation p.
GR in the octapeptide domain of the transcription factor PAX2 [ ]. Trionfini et al. Forbes et al. Proband organoid tubules demonstrated shortened, club-shaped primary cilia, whereas gene correction rescued this phenotype [ ]. Likewise, genetic correction of the single amino acid mutation of iPSCs generated from a congenital nephrotic syndrome patient due to NPHS1 mutations has restored nephrin localization and phosphorylation and slit diaphragm formation [ 74 ]. Firstly, MSCs can be readily expanded in culture, generating a large number of therapeutic doses.
Secondly, MSCs do not express blood group, DR antigens, and costimulatory CD40, CD80, and CD86 proteins to render them hypoimmunogenic, thus facilitating their safe use in allogeneic off-the-shelf protocols [ ]. Although a uniform mechanism governing the MSC-based therapy has not yet been discovered, available data have revealed several working models that promoted their use Fig.
The priority of MSCs to traffic to the sites of ischemia, hypoxia, and inflammatory response following injury plays a crucial role in the success of these as cellular therapy for organ injuries. MSC homing is defined as the arrest of MSCs within the vasculature of a tissue followed by transmigration across the endothelium [ , , ].
The homing of MSCs to the injured tissues has been driven by a combination of chemokine release from the injured tissue and chemokine receptors that are expressed by MSCs [ ]. CDhyaluronic acid CDHA interactions are involved in the process of homing of MSCs to the damaged renal tissue and promote renal function repair following acute tubular injury and chronic renal failure [ ].
Due to their vitality in enhancing the kidney-directional migration of transplanted MSCs for increasing the efficiency of tissue repair, some novel preconditioning strategies were explored, including incubation with cytokines or chemical compounds [ , , ], co-injection [ , ], hypoxia stimulation [ ], and genetic modifications [ , ].
Also, pulse-focused ultrasound pFUS has elicited local molecular responses through mechanotransduction, thus enhancing the renal homing of circulating MSCs [ , , ]. Treatment with intravenous injection of MSCs has efficiently induced improvement of the repaired kidney both morphologically and functionally.
Therapeutic properties of MSCs were originally derived from their engraftment in the injured kidney and subsequent transdifferentiation of MSCs into renal-specific cells to repopulate the kidney.
The possible role of MSCs in response to kidney injury was first observed when the female kidney transplants were transferred into male recipients, in which the Y chromosome staining of tubular epithelial cells was found [ , ].
Several studies have shown that intravenous injection of MSCs homed to the repaired kidney site and localized in the context of tubular epithelial lining and expressed the epithelial markers, indicating engraftment of MSCs [ 8 , , , ]. Although MSCs home to the injured sites of kidney via blood circulation after transplantation, the renal MSC engraftment was scarce and transient.
Most of injected MSCs remain in other blood-rich organs, such as the lung, liver, and spleen. All these facts suggest that the effects of MSCs may be mediated by another mechanism. These studies showed consistent results, in which MSC-conditioned media improved the survival of human proximal tubular cells when exposed to cisplatin in vitro [ 10 , , ]. Now, there is a growing consensus that kidney-protective effects of MSCs are primarily exerted by their paracrine function rather than by direct engraftment.
These contribute in renal protection by promoting proliferation of epithelial cells and angiogenesis, anti-apoptosis, anti-inflammatory, anti-fibrosis, and other signaling pathways [ 10 , , , ]. Moreover, accumulating evidence also underlined the paracrine actions mediated by extracellular vesicles EVs , small anuclear membrane-bound particles released from MSCs as a paracrine vehicle to deliver messenger RNA mRNA , microRNAs, proteins, or bioactive lipids that may reprogram the injured cells or induce secretion of cytoprotective factors [ , ].
Bruno et al. Similar results were obtained by Gatti et al. Eirin and his colleagues have tested the therapeutic effects of EVs in a porcine model with coexistence of RVD and metabolic syndrome. Moreover, MSC-derived EVs inhibited and reverted fibrosis progression in a diabetic nephropathy mouse model by downregulating fibrosis-related genes [ ]. The crosstalk and interplay of MSCs and local environment reversely control and regulate the paracrine activity of MSCs.
MSC growth conditions such as oxygen tension, growth factor composition, and mechanical properties may serve to directly influence paracrine activity [ , ].
As the paracrine of MSCs is affected by microenvironment structure, the therapeutic potential of their secretome can be manipulated in an engineered setting. MSCs comprise immunomodulatory and tolerogenic properties. Extensive in vitro and in vivo studies have demonstrated that MSCs are capable of suppressing T cell proliferation, influencing dendritic cell maturation and function, suppressing B cell proliferation and terminal differentiation, and modulating other immune cells such as natural killer NK cells and macrophages.
Besides, MSCs also induce regulatory T cells Tregs and maintain the capability of Tregs to suppress self-reactive T-effector responses [ ]. The immunosuppressive capacity of MSCs allows them to act as a potential therapeutic target in renal transplantation as they may inhibit allograft rejection and induce transplant tolerance [ , ].
The study conducted by Jang et al. Dental tissue-derived MSCs are also effective in reducing kidney glomerular lesion and perivascular inflammation infiltration [ ]. However, some studies failed to show a positive effect of the treatment with MSCs, and for some aspects, even deleterious results seem to be observed [ ].
Despite promising preclinical results obtained in animal models, which indicated effectiveness of MSCs in reducing acute and chronic kidney injuries, clinical trials still remained in the early phases and largely aimed to investigate the safety and efficacy of MSC infusion.
To date, more than 40 clinical trials were conducted worldwide, completed or ongoing, involving the use of MSCs in the treatment of kidney diseases as reported by the US National Institute of Health database ClinicalTrials.
According to the clinical study conducted by Gooch et al. A recent phase 2, randomized, double-blind, placebo-controlled trial conducted by Swaminathan et al. No significant difference was observed in the time to recovery of kidney function after treatment of early postoperative AKI with allogeneic MSCs when compared to those treated with placebo [ ].
The absence of a significant recovery signal after AKI in patients treated with MSCs might be attributable to several factors. Many patients in this study had impaired kidney function before surgery, and in the setting of already compromised kidney function, beneficial effects of MSCs could be attenuated.
What is more, the complexity of postcardiac surgery clinical setting and postoperative course might hinder the ability to observe a modest clinical effect with MSCs or other agents.
A multicenter, randomized study demonstrated the safety of allogeneic mesenchymal precursor cell MPC infusion in diabetic nephropathy. But no improvement in glomerular filtration rate has been observed [ ]. Similarly, another month study showed no significant improvements in renal function of CKD patients who received MSC infusion [ ]. Saad et al. Numerous clinical studies have shown that allogeneic MSC transplantation in patients with SLE resulted in the amelioration of disease activity, improvement in serological markers, and stabilization of renal function [ , , , ].
A single-center study involving 81 Chinese patients with active and refractory LN reported that Proteinuria levels were improved dramatically during the first month after treatment, and the ameliorations were sustained throughout the 9-month follow-up period [ ]. Given the immune-regulatory properties, MSCs have been administered to kidney transplant recipients, with the aim of controlling the host immune response towards the graft and minimizing immunosuppression, possibly leading to transplant tolerance.
A previous study conducted by Perico et al. Kidney biopsy revealed infiltration of immune cells with C3 deposits. It is hypothesized that kidney transplantation triggered graft inflammation, causing recruitment of MSCs to the graft and favoring differentiation of MSCs towards a proinflammatory phenotype [ ]. Perico et al. All MSC-treated patients had stable graft function during a 5—7-year follow-up, without increasing the susceptibility to infections or malignancy [ , ].
Erpicum et al. Clinical researches conducted by Mudrabettu et al. Notably, administration of MSCs has the potential to reduce the usage of immunosuppressants. It is widely accepted that embryonic renal SCs with nephrogenic potential would deplete soon after mice or several weeks before humans birth.
Interestingly, at least cells derived from different nephron segments are lost every hour in the urine, suggesting that the progenitor cells are required for continuous replacement of loss of cells during physiological processes [ ].
Additional evidence from several studies indicated that adult kidney upon acute or chronic injury has some ability to survive injury and undergo structural remodeling or repair, supporting that it has certain potential to retain regeneration.
To our knowledge, there is no single bona fide marker specific for RSPCs at present. Various attempts have been made to identify and characterize RSPCs from differentiated cells in adult kidney, including label-retaining assays, flow cytometry using cell surface markers, and side population assays.
In general, SCs have a slow turnover rate and display minimal physiologic differentiation. When labeled nucleic acids were incorporated, BrdU or 3H-thymidine, SCs retain the label for longer periods of time, while other cells lose [ ]. Maeshima and colleagues have first demonstrated the existence of LRCs in renal tubuli of normal rat kidneys. Oliver et al. These cells form spheres in vitro as well as potentially differentiate towards other lineages [ ]. LRCs formed tubule-like structure in 3D culture system and, when LRCs were injected into cultured metanephros, formed nephrons and collecting ducts [ ].
The drawback of this technique is that the labels such as BrdU might be released from the dying cells and were taken up from the adjacent dividing cells [ ]. Other selection strategies based on functional assays were utilized to identify and select RSPCs from human renal tissue. With the ability to effectively efflux the Hoechst dye, RSPCs can be detected via flow cytometry and are termed as the side population SP cells, which were found in murine kidney interstitial space in several groups [ , , , ].
Aldehyde dehydrogenase ALDH activity was used to isolate cells with progenitor characteristics from adult human renal cortical tissue. Although these cells were identified using a different strategy and were localized in different nephron segments, these all exhibited the capacity to self-renew and the ability to differentiate towards renal tubules or podocytes and different lineages.
Experiments in rat and mouse models of tubular or glomerular damage suggested a therapeutic effect of adult RSPCs of different types and sites of origin. The mechanism of RSPCs involved in kidney repair is associated to integrate into nephrons and is in parallel to a paracrine mechanism based on renoprotective molecules.
The activated RSPCs would differentiate along a particular cell lineage and replace the damaged kidney cells. During acute kidney injury, the LRCs in the papilla migrated to the upper papilla and formed a compartment of rapidly proliferating cells, which may play a role in repair after ischemic injury [ ]. The eventual descendants of LRCs differentiated into epithelial cells [ ]. Shen et al. As expected, intravenously infused iEPCs were recruited to the injured kidney, replaced injured endothelial cells, and relieve kidney damage in AKI mice.
In addition, the injection of kidney SP cells into the AKI model demonstrated the recovery of renal function [ , ]. However, some studies did not observe significant renal integration of SP cells and differentiation into renal cells was not observed as expected in some studies [ , ].
Bussolati et al. Aggarwal et al. Hishikawa and colleagues have reported that the SP cells isolated from the kidney with acute renal failure expressed high levels of renoprotective factors, such as HGF, VEGF, and leukemia inhibitory factor [ ]. Also, the exosomes from conditioned medium of urine-derived stem cells USCs-Exo might have the potential to prevent kidney injury from diabetes by inhibiting podocyte apoptosis and promoting vascular regeneration and cell survival [ ].
Since these cells could be conveniently obtained through non-invasive methods, urine-derived RSPCs possessed great potential in cell therapy and tissue regeneration. Furthermore, the release of pro-active renal protective factors from distal sites might also be involved, and this is because the intravenously injected RSPCs were localized in extrarenal organs such as the lungs and liver.
Despite the important role played in the repair and regeneration of damaged kidney tissue, a study showed that the dysregulated proliferation of renal progenitor cells generates hyperplastic glomerular lesions, scarring, and nephron loss eventually leading to degenerative disease such as crescentic nephritis or collapsing glomerulopathy [ ].
Kusaba et al. In their study, injury to proximal epithelial tubule induced expression of markers of putative epithelial SCs in human kidney CD24, CD, and vimentin. What is more, no dilution of fate marker was observed when mice with completely labeled kidneys were subjected to injury and repair, indicating that unlabeled progenitors do not contribute to kidney repair [ ].
Berger and colleagues have also suggested that there is no fixed progenitor cell population in the kidney, and tubular cells transiently acquire the phenotype of progenitor cells with reparative characteristics following injury [ ]. Stem cells have shown great potential in kidney injury repair and disease treatment, but some pressing issues remain to be resolved before the clinical application.
ESCs have limited clinical application due to ethical issues regarding their origin, tumorigenicity after transplantation. As the donor cells most likely do not originate from the recipient patient, immunological rejection of the cells differentiated from ESCs upon allogeneic cell transplantation remains a major challenge for cell therapy.
Simultaneous administration of immunosuppressive drugs can aid in overcoming these problems but can induce serious side effects [ ]. However, it is a labor-intensive, time-consuming work that is hard to carry out [ ]. When it comes to iPSCs, the highly proliferative nature and the use of viral vectors for reprogramming exist with the risk of tumor development following transplantation, although some safer approaches such as the use of small molecules either have less reprogramming efficiency or usually cannot induce pluripotency alone.
Reprogramming factors used to induce pluripotency in particular, the proto-oncogenes c-MYC and KLF4 may become re-activated in the transplanted cells differentiated from iPSCs [ ]. Moreover, frustrations due to low replication rate and premature aging were encountered in the administration of iPSCs.
Despite considerable body of evidence in in vitro supports the usefulness of MSCs, controversies about the use of SCs still persist. In clinical trials, the improvement of renal function and structure induced by MSCs in clinical trials is not as obvious as expected. The main reasons for the limited clinical efficacy were the low engraftment, the poor survival rate, and the impaired paracrine capacity of injected cells in vivo. The majority of grafted MSCs might be trapped in the lungs, liver, and spleen.
To improve the beneficial effects of MSC transplantation, the efficient strategy of administration of MSC needs to be discussed. Liu et al. As the lack of inflammation in the early injured kidney was favorable for MSC survival within the tissue, favorable expression of homing adhesion molecules ICAM-1 and VCAM-1 were present, further promoting MSCs to integrate into injured kidney tissue [ ].
In contrast, Casiraghi et al. Therefore, the optimal timing of MSC administration for different kidney diseases remains under discussion. With more warnings, a long-term examination of intrarenal injection of MSCs in progressive rat model of glomerulonephritis has reported an abnormal and detrimental adipogenic differentiation of MSCs, suggesting the potential harm of administration of MSCs [ ].
With regard to RSPCs, which showed the priority in displaying the inherent patient specificity at genomic level and kidney-specific epigenetic changes, the tissues from which autologous RSPCs can be obtained are poorly accessible or insufficient for cell isolation.
The immune rejection of stem cell injection is another challenge that hinders the clinical application of stem cell-based therapy. The allogeneic cells derived from hESCs will be robustly immune rejected by the recipient due to the direct activation of T cells by the foreign MHCs.
While the patient-specific iPSCs share the same genetic background, and their derivatives might have a better chance to be immune tolerated, the genomic instability and abnormal epigenetics associated with iPSCs can induce immunogenicity in some cells of their derivatives [ ].
Recent advances in cell-based therapy using various cell sources have demonstrated great promise towards restoring normal kidney functions in the AKI, DN, and CKD models, etc. The kidney organoids induced by stem cells provide the authentic and practical models for investigating kidney development and disease and progressing understanding about tissue regeneration, drug screening, and disease modeling.
Although the stem cells from different sources show great promise as therapeutic agents for kidney diseases, the amount of research currently available is insufficient to achieve the docking of different kidney diseases with the most suitable transplanted stem cells.
The Center for Regenerative Medicine prioritizes new therapies that can be adopted by the practice. The changes in blood flow, oxygenation and function suggest that small vessels are being formed or reopened in the kidney after stem cell therapy," says Dr. Atherosclerotic renovascular disease is a hardening and narrowing of arteries that deliver blood to the kidneys.
Low blood flow damages tissue, causing chronic kidney disease and eventually end-stage renal failure. Patients then require kidney dialysis. There are limited therapeutic options for reversing kidney damage from vascular disease.
In a phase 1 clinical trial, Dr. Textor's team studied 39 patients with atherosclerotic renovascular disease on two occasions over three months. Researchers infused 21 patients each with mesenchymal stem cells derived from the patient's own fat.
Delivered directly into the renal artery of the damaged kidney, the mesenchymal stem cell therapy was given in three different dose amounts. Researchers measured kidney function, oxygen levels, blood flow and markers of injury before the stem cell therapy and three months after infusion. Those data were compared to 18 patients with atherosclerotic renovascular disease treated only with standard therapies.
Additional studies will be needed to verify the findings and address whether stem cell therapy could repair common forms of kidney damage, such as damage from diabetes.
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