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Allogeneic and autologous mode of stem cell transplantation in regenerative medicine: which way to go?

Mamidi MK, Dutta S, Bhonde R, Das AK, Pal R

Med Hypotheses, 2014 Dec;83(6):787-91.
PMID: 25456787 DOI: 10.1016/j.mehy.2014.10.010

Stem cell transplantation is a generic term covering different techniques. However there is argument over the pros and cons of autologous and allogeneic transplants of mesenchymal stem cells (MSCs) for regenerative therapy. Given that the MSCs have already been proven to be safe in patients, we hypothesize that allogeneic transplantation could be more effective and cost-effective as compared to autologous transplantation specifically in older subjects who are the likely victims of degenerative diseases. This analysis is based on the scientific logic that allogeneic stem cells extracted in large numbers from young and healthy donors could be physiologically, metabolically and genetically more stable. Therefore stem cells from young donors may be expected to exhibit higher vigor in secreting trophic factors leading to activation of host tissue-specific stem cells and also be more efficient in remodeling the micro-environmental niche of damaged tissue.

Matched MeSH terms: Hematopoietic Stem Cell Transplantation/economics; Hematopoietic Stem Cell Transplantation/methods; Stem Cell Transplantation/economics; Stem Cell Transplantation/methods*
Isolation of purified autologous peripheral blood CD34+ cells with low T cell content using CliniMACS device--a local experience

Leong CF, Habsah A, Teh HS, Goh KY, Fadilah SA, Cheong SK

Malays J Pathol, 2008 Jun;30(1):31-6.
PMID: 19108409

Peripheral blood stem cells (PBSC) mobilised with growth factor with or without chemotherapeutic regimens, are used increasingly in both autologous and allogeneic transplantation. Previously, many PBSC harvests are used directly without ex vivo manipulation, and these PBSC have been shown to be contaminated with tumour cells, which may contribute to subsequent relapses post transplantation. Therefore, requirement for purging of malignant cells from the harvest has initiated the use of various methods to reduce tumour cell contamination of the graft by the positive selection of CD34+ progenitor cells or negative selection of tumour cells using other cell-specific antigens. We report here our local experience with the CliniMACS (magnetic-activated cell separation system) in eight adult patients with haematologic malignancies.

Matched MeSH terms: Hematopoietic Stem Cell Transplantation/instrumentation; Hematopoietic Stem Cell Transplantation/methods; Peripheral Blood Stem Cell Transplantation/instrumentation; Peripheral Blood Stem Cell Transplantation/methods*
Posterolateral spinal fusion with ostegenesis induced BMSC seeded TCP/HA in a sheep model

Shamsul BS, Tan KK, Chen HC, Aminuddin BS, Ruszymah BH

Tissue Cell, 2014 Apr;46(2):152-8.
PMID: 24630213 DOI: 10.1016/j.tice.2014.02.001

Autogenous bone graft is the gold standard for fusion procedure. However, pain at donor site and inconsistent outcome have left a surgeon to venture into some other technique for spinal fusion. The objective of this study was to determine whether osteogenesis induced bone marrow stem cells with the combination of ceramics granules (HA or TCP/HA), and fibrin could serve as an alternative to generate spinal fusion. The sheep's bone marrow mesenchymal stem cells (BMSCs) were aspirated form iliac crest and cultured for several passages until confluence. BMSCs were trypsinized and seeded on hydroxyapatite scaffold (HA) and tricalcium phosphate/hydroxyapatite (TCP/HA) for further osteogenic differentiation in the osteogenic medium one week before implantation. Six adult sheep underwent three-level, bilateral, posterolateral intertransverse process fusions at L1-L6. Three fusion sites in each animal were assigned to three treatments: (a) HA constructs group/L1-L2, (b) TCP/HA constructs group/L2-L3, and (c) autogenous bone graft group/L5-L6. The spinal fusion segments were evaluated using radiography, manual palpation, histological analysis and scanning electron microscopy (SEM) 12 weeks post implantation. The TCP/HA constructs achieved superior lumbar intertransverse fusion compared to HA construct but autogenous bone graft still produced the best fusion among all.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation*
Fulltext The rabbit as a model for studying lung disease and stem cell therapy

Kamaruzaman NA, Kardia E, Kamaldin N', Latahir AZ, Yahaya BH

Biomed Res Int, 2013;2013:691830.
PMID: 23653896 DOI: 10.1155/2013/691830

No single animal model can reproduce all of the human features of both acute and chronic lung diseases. However, the rabbit is a reliable model and clinically relevant facsimile of human disease. The similarities between rabbits and humans in terms of airway anatomy and responses to inflammatory mediators highlight the value of this species in the investigation of lung disease pathophysiology and in the development of therapeutic agents. The inflammatory responses shown by the rabbit model, especially in the case of asthma, are comparable with those that occur in humans. The allergic rabbit model has been used extensively in drug screening tests, and this model and humans appear to be sensitive to similar drugs. In addition, recent studies have shown that the rabbit serves as a good platform for cell delivery for the purpose of stem-cell-based therapy.

Matched MeSH terms: Stem Cell Transplantation*
Treatment viability of stem cells in ophthalmology

Jeganathan VS, Palanisamy M

Curr Opin Ophthalmol, 2010 May;21(3):213-7.
PMID: 20393292 DOI: 10.1097/ICU.0b013e32833867ad

Adult ocular stem cells have the potential to restore vision in patients previously deemed incurable. This review summarizes strides in stem cell research and stumbling blocks that must be overcome to enable treatment viability in ophthalmology.

Matched MeSH terms: Stem Cell Transplantation*
Current status and prospective application of stem cell-based therapies for spinal cord injury

Das AK, Gopurappilly R, Parhar I

Curr Stem Cell Res Ther, 2011 Jun;6(2):93-104.
PMID: 21190537

Spinal cord injuries (SCIs) are a common form of trauma that leaves a huge trail of morbidity and human suffering in its wake. They occur mostly among the young, causing severe physical, psychological, social and economic burdens. The treatment of this condition has rather been disappointing; most of the management strategies being mainly supportive and prophylactic. In recent years there has been an emerging interest in the use of stem cells to regenerate the nervous tissue that has been damaged or lost. Although there has been much hype and unfounded hope, modest successes have been witnessed, and it is possible that these therapeutic strategies may have much more to offer in the future. This paper will review the current strategies of exploring cell-based therapies, mainly different types of stem cells to treat SCI along with the evidence that has been accumulated over the past decade in a rational bench-to-bedside approach. Furthermore, critical aspects such as the mode of delivery and ethical considerations are also discussed along with feasible suggestions for future translational research to provide a contextual picture of the current state of advancements in this field. The impediments to regeneration in the site of injury are briefly explained along with the benefits and drawbacks of different cell types used in the treatment of this condition. We hope that this review will offer a significant insight into this challenging clinical condition.

Matched MeSH terms: Stem Cell Transplantation*
Microfluidic chip-based assay for post-hematopoietic stem cell transplantation chimerism monitoring using polymorphic tandem repeat markers

Daud SS, Ibrahim K, Choong SS, Vengidasan L, Chong LA, Ariffin H

Anal Biochem, 2010 Feb 15;397(2):181-5.
PMID: 19822126 DOI: 10.1016/j.ab.2009.10.008

Following hematopoietic stem cell transplantation (HSCT), it is important to determine whether engraftment is successful and to track the dynamic changes of the graft. Tandem repeats such as minisatellites and microsatellites are currently the most established markers for chimerism application. We have developed a reliable method to quantitatively evaluate engraftment status in post-allogeneic HSCT patients using variable number of tandem repeat (VNTR) markers and "lab-on-a-chip" microfluidic electrophoresis technology. Following identification of an informative marker by conventional polymerase chain reaction (PCR), donor chimerism percentage was calculated based on a standard curve generated from artificially mixed patient-donor DNA-specific alleles in serial dilutions. All PCR products were mixed with commercial gel dye and loaded into Agilent DNA 1000 microfluidic LabChips for DNA sizing and quantitation. In 44 patients, separation of pretransplant and donor DNA fragments was resolved clearly and accomplished rapidly within 30min. Chimerism analysis using this platform is able to detect an amount as low as 6.3% donor DNA with acceptable coefficient of variation values. We also demonstrated concordant chimerism analysis findings using both microchip tandem repeats and real-time PCR quantitation of insertion-deletion polymorphisms. This microchip platform obviates the need for fluorescently labeled primers or any post-PCR sample manipulation. Quantitative monitoring of post-HSCT chimerism status using microfluidic electrophoresis is a useful tool for both large- and small-scale post-HSCT chimerism centers.

Matched MeSH terms: Hematopoietic Stem Cell Transplantation/methods*
Fulltext VNTR markers for qualitative evaluation of engraftment in unrelated cord blood transplantations

Noor SM, Phipps ME, Fong MY, Chan LL

Med J Malaysia, 2007 Mar;62(1):23-6.
PMID: 17682565 MyJurnal

Allogeneic stem cell transplantation is a treatment option for malignant and non-malignant disorders in children. For children with no HLA-matched sibling or related stem cell donors, there is the option of unrelated cord blood donors. At the University of Malaya Medical Centre (UMMC) in Kuala Lumpur, the first unrelated cord blood transplantation (CBT) was performed in October 1997. All unrelated CBT performed in UMMC relied on cord blood units imported from overseas. DNA typing with variable number of tandem repeat (VNTR) loci was done to qualitatively evaluate engraftment in 15 unrelated CBT. In all the fifteen cases that were evaluated, molecular evidence of engraftment or non-engraftment correlated with the clinical findings.

Matched MeSH terms: Cord Blood Stem Cell Transplantation*
Stem cells and injectable hydrogels: Synergistic therapeutics in myocardial repair

Sepantafar M, Maheronnaghsh R, Mohammadi H, Rajabi-Zeleti S, Annabi N, Aghdami N, et al.

Biotechnol Adv, 2016 Jul-Aug;34(4):362-379.
PMID: 26976812 DOI: 10.1016/j.biotechadv.2016.03.003

One of the major problems in the treatment of cardiovascular diseases is the inability of myocardium to self-regenerate. Current therapies are unable to restore the heart's function after myocardial infarction. Myocardial tissue engineering is potentially a key approach to regenerate damaged heart muscle. Myocardial patches are applied surgically, whereas injectable hydrogels provide effective minimally invasive approaches to recover functional myocardium. These hydrogels are easily administered and can be either cell free or loaded with bioactive agents and/or cardiac stem cells, which may apply paracrine effects. The aim of this review is to investigate the advantages and disadvantages of injectable stem cell-laden hydrogels and highlight their potential applications for myocardium repair.

Matched MeSH terms: Stem Cell Transplantation*
Fulltext Providing a cure for beta thalassaemia major

Chan LL, Lin HP, Ariffin WA, Ariffin H

Med J Malaysia, 2001 Dec;56(4):435-40.
PMID: 12014762

The current treatment options for beta thalassaemia major patients include conservative treatment with blood cell transfusions and iron chelation or stem cell transplantation. Regular blood transfusions inevitably lead to multi-organ haemosiderosis and are attended by risks of blood-borne infections. Results from stem cell transplantation are good and suggest that this should be offered as first line therapy when a matched sibling donor is available because the patient is often cured and able to live a normal life. Of 38 Malaysian children who underwent bone marrow or cord blood transplantations using matched sibling donors, 29 (76%) are now cured.

Matched MeSH terms: Hematopoietic Stem Cell Transplantation*
Fulltext Treating high risk childhood solid tumours with autologous peripheral blood stem cell transplantation--early experience in University Hospital, Kuala Lumpur

Chan LL, Lin HP, Ariffin WA, Ariffin H, Saw MH

Med J Malaysia, 1999 Jun;54(2):175-9.
PMID: 10972026

Although survival rates for childhood cancers have improved steadily over the past two decades, the outcome for advanced stage solid tumours remains poor. Many of these tumours are chemosensitive but most chemotherapeutic regimens are limited by their haematological toxicities. Much attention is now focused on mega-dose chemotherapy followed by stem cell rescue in the treatment of disseminated neuroblastoma, rhabdomyosarcoma, germ cell tumour and brain tumours. There is a preferential shift towards peripheral blood stem cell transplantation instead of bone marrow transplantation because of its advantages of faster engraftment, decreased transfusion and antibiotic usage and shortened hospitalisation. This mode of therapy is dependent on technologies including peripheral blood stem cell harvesting, cell cryopreservation and thawing. These technologies were recently made available in Malaysia and we report our early experience.

Matched MeSH terms: Hematopoietic Stem Cell Transplantation*
Outcomes of high dose therapy and autologous haematopoietic stem cell transplantation for non-hodgkin lymphoma: A retrospective analysis in a resource-limited country

Anuar NA, Tey KWF, Ng SC, Teh AKH, Abdul Rahman MHF, Chong BP, et al.

Int J Clin Pract, 2021 Mar;75(3):e13823.
PMID: 33202073 DOI: 10.1111/ijcp.13823

AIM: To retrospectively report the clinical outcomes of non-Hodgkin's Lymphoma (NHL) patients post high dose therapy (HDT) with autologous haematopoietic stem cell transplant (AHSCT) and determine whether upfront transplant, which is a first-line consolidative treatment with induction chemotherapy, would be a feasible modality in a resource-limited country.
METHODS: The medical records for NHL patients who had undergone HDT followed by AHSCT from October 1997 to November 2016 from two hospitals in Klang Valley, Malaysia were obtained from the medical record database and analysed retrospectively through statistical analysis.
RESULTS: A total of 148 patients were retrospectively identified post-AHSCT, where the majority of whom had B cell lymphoma (53.4%). Majority of patients (88.5%) were in complete remission before AHSCT. The overall survival (OS) and event-free survival (EFS) at 3 years were 68.9% and 60.8%, respectively. The major cause of death was disease progression at 73.9%, while transplant-related mortality was 15.2%, with a median follow-up period of 179.5 weeks.
CONCLUSION: Our study illustrates the promising outcomes of HDT with AHSCT in NHL patients in a resource-limited country. We recommend larger studies to be conducted in the future with a longer duration of follow-up to validate our findings.

Matched MeSH terms: Hematopoietic Stem Cell Transplantation*
Long-Term Monitoring of Donor Xenogeneic Testis Tissue Grafts and Cell Implants in Recipient Mice Using Ultrasound Biomicroscopy

Fayaz MA, Awang-Junaidi AH, Singh J, Honaramooz A

Ultrasound Med Biol, 2020 11;46(11):3088-3103.
PMID: 32800471 DOI: 10.1016/j.ultrasmedbio.2020.07.010

Testis tissue xenografting and testis cell aggregate implantation from various donor species into recipient mice are novel models for the study and manipulation of testis formation and function in target species. Thus far, the analysis of such studies has been limited to surgical or post-mortem retrieval of samples. Here we used ultrasound biomicroscopy (UBM) to monitor the development of neonatal porcine testis grafts and implants in host mice for 24 wk, and to correlate UBM and (immuno)histologic changes. This led to long-term visualization of gradual changes in volume, dimension and structure of grafts and implants; detection of a 4 wk developmental gap between grafts and implants; and revelation of differences in implant development depending on the craniocaudal site of implantation on the back of host mice. Our data support the reliability and precision of UBM for longitudinal study of transplants, which eliminates the need for frequent surgical sampling.

Matched MeSH terms: Cell Transplantation*
HLA-B*38:64, an HLA-B*38 variant, detected in a Singaporean Malay unrelated hematopoietic stem cell donor

Cho L, Kaur A, Cereb N, Lin PY, Yang KL

HLA, 2020 08;96(2):217-218.
PMID: 32227685 DOI: 10.1111/tan.13873

One nucleotide substitution in codon 89 of HLA-B*38:02:01:01 results in a novel allele, HLA-B*38:64.

Matched MeSH terms: Hematopoietic Stem Cell Transplantation*
Discovery of HLA-B*35:368, a novel HLA-B*35 variant, in a Singaporean Malay hematopoietic stem cell donor

Kaur A, Cho L, Cereb N, Lin PY, Yang KL

HLA, 2020 07;96(1):94-95.
PMID: 32166893 DOI: 10.1111/tan.13862

DNA substitutions from codons 69 to 71 of HLA-B*35:05:01:01 result in a novel allele, HLA-B*35:368.

Matched MeSH terms: Hematopoietic Stem Cell Transplantation*
Haematopoietic stem cell transplantation for inborn errors of immunity: 25-year experience from University of Malaya Medical Centre, Malaysia

Ariffin H, Ab Rahman S, Jawin V, Foo JC, Amram NF, Mahmood NM, et al.

J Paediatr Child Health, 2020 Mar;56(3):379-383.
PMID: 31479560 DOI: 10.1111/jpc.14621

AIM: Inborn errors of immunity (IEI) comprise a heterogeneous group of disorders of the immune system, most of which are curable by haematopoietic stem cell transplantation (HSCT). We present a 25-year audit of HSCT for IEI at a tertiary-level academic hospital in Malaysia.
METHODS: Review of medical records of all cases of IEI who underwent HSCT between January 1993 and December 2018 at our centre. Diagnoses, complications, HSCT protocols and outcome data were studied.
RESULTS: There were 20 patients (19 boys) with a median age at diagnosis of 11 months (range: 2 months to 12 years). Eleven of 19 (58%) had malnutrition at presentation. Donor sources were variable: 13 (65%) matched sibling donor (MSD), 4 (20%) human leukocyte antigen-haploidentical donor (HD) and 3 (15%) matched unrelated donor (MUD). Conditioning regimens were physician-dependent and adapted to each patient's clinical status. Grades III-IV acute graft-versus-host disease occurred in two of three cases who received MUD grafts, 50% in those who received HD, and 8% in the MSD group. Transplant-related mortality at day +100 was 5%. With a median follow-up of 7.5 years, 18 (90%) patients are alive and free of infections.
CONCLUSION: Outcome of HSCT for IEI in our centre is comparable with international reports. HSCT results using HD and MUD grafts are also good despite challenges from acute graft-versus-host disease, providing a feasible alternative for patients without matched donors.

Matched MeSH terms: Hematopoietic Stem Cell Transplantation*
The use of mesenchymal stromal cells in treatment of lung disorders

Kardia E, Zakaria N, Sarmiza Abdul Halim NS, Widera D, Yahaya BH

Regen Med, 2017 03;12(2):203-216.
PMID: 28244823 DOI: 10.2217/rme-2016-0112

The therapeutic use of mesenchymal stromal cells (MSCs) represents a promising alternative clinical strategy for treating acute and chronic lung disorders. Several preclinical reports demonstrated that MSCs can secrete multiple paracrine factors and that their immunomodulatory properties can support endothelial and epithelial regeneration, modulate the inflammatory cascade and protect lungs from damage. The effects of MSC transplantation into patients suffering from lung diseases should be fully evaluated through careful assessment of safety and associated risks, which is a prerequisite for translation of preclinical research into clinical practice. In this article, we summarize the current status of preclinical research and review initial MSC-based clinical trials for treating lung injuries and lung disorders.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation*
The potential role of mesenchymal stem cells in modulating antiageing process

Govindasamy V, Rajendran A, Lee ZX, Ooi GC, Then KY, Then KL, et al.

Cell Biol Int, 2021 Oct;45(10):1999-2016.
PMID: 34245637 DOI: 10.1002/cbin.11652

Ageing and age-related diseases share some basic origin that largely converges on inflammation. Precisely, it boils down to a common pathway characterised by the appearance of a fair amount of proinflammatory cytokines known as inflammageing. Among the proposed treatment for antiageing, MSCs gained attention in recent years. Since mesenchymal stem cells (MSCs) can differentiate itself into a myriad of terminal cells, previously it was believed that these cells migrate to the site of injury and perform their therapeutic effect. However, with the more recent discovery of huge amounts of paracrine factors secreted by MSCs, it is now widely accepted that these cells do not engraft upon transplantation but rather unveil their benefits through excretion of bioactive molecules namely those involved in inflammatory and immunomodulatory activities. Conversely, the true function of these paracrine changes has not been thoroughly investigated all these years. Hence, this review will describe in detail on ways MSCs may capitalize its paracrine properties in modulating antiageing process. Through a comprehensive literature search various elements in the antiageing process, we aim to provide a novel treatment perspective of MSCs in antiageing related clinical conditions.

Matched MeSH terms: Mesenchymal Stem Cell Transplantation/methods*
Stem cells differentiation and probing their therapeutic applications in hematological disorders: a critical review

Ali F, Taresh S, Al-Nuzaily M, Mok PL, Ismail A, Ahmad S

Eur Rev Med Pharmacol Sci, 2016 Oct;20(20):4390-4400.
PMID: 27831631

Numerous lines of evidence support that bone marrow is a rich source of stem cells that can be used for research purposes and to treat some complex blood diseases and cancers. Stem cells are a potential source for regenerative medicine and tissue replacement after injury or disease, and mother cells that possess the capacity to become any type of cell in the body. They are cells without specific structure and characterized by their ability to self-renew or multiply while maintaining the potential to develop into other types of cells. Stem cells can normally become cells of the blood, heart, bones, skin, muscles or brain. Although, there are different sources of stem cells, all types of stem cells have the same capacity to develop into multiple types of cells. Stem cells are generally described as unspecialized cells with unlimited proliferation capacity that can divide (through mitosis) to produce more stem cells. Several types of adult stem cells have been characterized and can be cultured in vitro, including neural stem cells, hematopoietic stem cells, mesenchymal stem cells, cardiac stem cells and epithelial stem cells. They are valuable as research tools and might, in the future, be used to treat a wide range of diseases such as hematological hereditary diseases, Parkinson's disease, diabetes mellitus, heart disease and many other diseases. Currently, two types of stem cells have been identified based on their origins, namely embryonic stem cells and adult stem cells. Collectively, although many kinds of literature have been studying stem cell application in terms of clinical practice, stem cell-based therapy is still in its infancy stage.

Matched MeSH terms: Stem Cell Transplantation*
Fulltext Advances in hematopoietic stem cell transplantation in the Asia-Pacific region: the second report from APBMT 2005-2015

Iida M, Kodera Y, Dodds A, Ho AYL, Nivison-Smith I, Akter MR, et al.

Bone Marrow Transplant, 2019 Dec;54(12):1973-1986.
PMID: 31089289 DOI: 10.1038/s41409-019-0554-9

Between 2005 and 2015, 138,165 hematopoietic stem cell transplantation (HSCT) were reported in 18 countries/regions in the Asia-Pacific region. In this report, we describe current trends in HSCT throughout the Asia-Pacific region and differences among nations in this region and various global registries. Since 2008, more than 10,000 HSCTs have been recorded each year by the Asia-Pacific Blood and Marrow Transplantation Group Data Center. Between 2005 and 2015, the greatest increase in the number of HSCTs was observed in Vietnam. Allogeneic HSCT was performed more frequently than autologous HSCT, and a majority of cases involved related donors. Regarding allogeneic HSCT, the use of cord blood has remained steady, especially in Japan, and the number of cases involving related HLA non-identical donors has increased rapidly, particularly in China. The incidence of hemoglobinopathy, a main indication for allogeneic HSCT in India, China, Iran, and Pakistan, increased nearly six-fold over the last decade. Among the 18 participating countries/regions, the transplant rate per population varied widely according to the absolute number of HSCTs and the national/regional population size. We believe that this report will not only benefit the AP region but will also provide information about HSCT to other regions worldwide.

Matched MeSH terms: Hematopoietic Stem Cell Transplantation/methods*

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