6. Therapy using tissue-specific stem cells

2021 ◽  
pp. 90-108
Author(s):  
Jonathan Slack
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Haematopoietic Stem Cell Transplantation ◽  
Genetic Diseases ◽  
Haematopoietic Stem Cell ◽  
Eye Injuries ◽  
Tissue Specific ◽  
Allogeneic Hsct ◽  
Tissue Specific Stem Cells

‘Therapy using tissue-specific stem cells’ begins with haematopoietic stem cell transplantation (HSCT), which is considered the most important type of stem cell therapy. HSCT covers the transplantation of bone marrow and other types of transplant where the blood-forming stem cells of the graft come from non-marrow sources. It is used mostly for the treatment of leukaemias and lymphomas. Some genetic diseases of the blood have also been successfully treated using allogeneic HSCT. There are also other examples of cell therapy using tissue-specific stem cells, such as epidermal cells for the treatment of burns and limbal (corneal) stem cells for treatment of eye injuries.

scholarly journals Study protocol of a pilot study evaluating feasibility and acceptability of a psychosexual intervention for couples postallogeneic haematopoietic stem cell transplantation

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e039300
Author(s):  
Brindha Pillay ◽  
Maria Ftanou ◽  
David Ritchie ◽  
Yvonne Panek-Hudson ◽  
Michael Jefford ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pilot Study ◽  
Sexual Dysfunction ◽  
Stem Cell Transplantation ◽  
Relationship Satisfaction ◽  
Cell Transplantation ◽  
Haematopoietic Stem Cell Transplantation ◽  
Haematopoietic Stem Cell ◽  
Post Transplantation ◽  
Allogeneic Hsct

IntroductionSexual dysfunction is one of the most common side effects of allogeneic haematopoietic stem cell transplantation (HSCT) for haematological cancers. Problems can persist between 5 and 10 years post-transplant and impact mood, couple intimacy and relationship satisfaction. Few intervention studies, however, target sexual dysfunction in patients post-HSCT. This pilot study aims to examine the feasibility and acceptability of implementing a psychosexual intervention for HSCT survivors and their partners post-transplantation.Methods and analysisFifteen allogeneic HSCT survivors and their partners will be recruited. Patients who are more than 3 months post-transplantation will be sent invitation letters describing the couples’ psychosexual intervention that will be offered through this study. The intervention will comprise two components: (1) psychosexual education about medical and behavioural treatment options for sexual dysfunction delivered by a haematology nurse consultant; (2) emotionally focused therapy-based relationship education programme for couples delivered by a clinical psychologist (four sessions of 1.5 hours each). Couples who consent to participate will be administered a series of measures assessing mood, relationship satisfaction and sexual dysfunction preintervention and post-intervention, as well as satisfaction with the intervention postintervention. Feasibility of the intervention will be examined via recording enrolment rate, adherence, compliance with completing outcome measures and fidelity of intervention delivery.Ethics and disseminationEthics approval has been obtained at the Peter MacCallum Cancer Centre in Melbourne, Australia. Results will be presented at national and international conferences and published in a peer-reviewed journal so that in can be accessed by clinicians involved in the care of allogeneic HSCT patients. If this intervention is found to be feasible and acceptable, its impact will be examined in a future randomised controlled trial and subsequently implemented as part of routine care in the allogeneic HSCT population.

scholarly journals Germline competent mesoderm: the substrate for vertebrate germline and somatic stem cells?

Biology Open ◽  
2021 ◽  
Vol 10 (10) ◽  
Author(s):  
Aaron M. Savage ◽  
Ramiro Alberio ◽  
Andrew D. Johnson
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Germ Cells ◽  
Molecular Mechanisms ◽  
Germ Plasm ◽  
Cell Types ◽  
Model Organisms ◽  
Developmental Potential ◽  
Tissue Specific ◽  
Tissue Specific Stem Cells

ABSTRACT In vitro production of tissue-specific stem cells [e.g. haematopoietic stem cells (HSCs)] is a key goal of regenerative medicine. However, recent efforts to produce fully functional tissue-specific stem cells have fallen short. One possible cause of shortcomings may be that model organisms used to characterize basic vertebrate embryology (Xenopus, zebrafish, chick) may employ molecular mechanisms for stem cell specification that are not conserved in humans, a prominent example being the specification of primordial germ cells (PGCs). Germ plasm irreversibly specifies PGCs in many models; however, it is not conserved in humans, which produce PGCs from tissue termed germline-competent mesoderm (GLCM). GLCM is not conserved in organisms containing germ plasm, or even in mice, but understanding its developmental potential could unlock successful production of other stem cell types. GLCM was first discovered in embryos from the axolotl and its conservation has since been demonstrated in pigs, which develop from a flat-disc embryo like humans. Together these findings suggest that GLCM is a conserved basal trait of vertebrate embryos. Moreover, the immortal nature of germ cells suggests that immortality is retained during GLCM specification; here we suggest that the demonstrated pluripotency of GLCM accounts for retention of immortality in somatic stem cell types as well. This article has an associated Future Leaders to Watch interview with the author of the paper.

Progress of Mesenchymal Stem Cell-Derived Exosomes in Tissue Repair

2020 ◽  
Vol 26 (17) ◽  
pp. 2022-2037 ◽  
Author(s):  
Guifang Zhao ◽  
Yiwen Ge ◽  
Chenyingnan Zhang ◽  
Leyi Zhang ◽  
Junjie Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Tissue Repair ◽  
Inflammatory Responses ◽  
Biologically Active ◽  
Research Progress ◽  
Tissue Specific

Mesenchymal stem cells (MSCs) are a kind of adult stem cells with self-replication and multidirectional differentiation, which can differentiate into tissue-specific cells under physiological conditions, maintaining tissue self-renewal and physiological functions. They play a role in the pathological condition by lateral differentiation into tissue-specific cells, replacing damaged tissue cells by playing the role of a regenerative medicine , or repairing damaged tissues through angiogenesis, thereby, regulating immune responses, inflammatory responses, and inhibiting apoptosis. It has become an important seed cell for tissue repair and organ reconstruction, and cell therapy based on MSCs has been widely used clinically. The study found that the probability of stem cells migrating to the damaged area after transplantation or differentiating into damaged cells is very low, so the researchers believe the leading role of stem cell transplantation for tissue repair is paracrine secretion, secreting growth factors, cytokines or other components. Exosomes are biologically active small vesicles secreted by MSCs. Recent studies have shown that they can transfer functional proteins, RNA, microRNAs, and lncRNAs between cells, and greatly reduce the immune response. Under the premise of promoting proliferation and inhibition of apoptosis, they play a repair role in tissue damage, which is caused by a variety of diseases. In this paper, the biological characteristics of exosomes (MSCs-exosomes) derived from mesenchymal stem cells, intercellular transport mechanisms, and their research progress in the field of stem cell therapy are reviewed.

Reduced-Intensity Conditioning Regimen in Allogeneic Haematopoietic Stem Cell Transplantation for Follicular Lymphoma and Chronic Lymphocytic Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4382-4382
Author(s):  
Carlos Pinho Vaz ◽  
Rosa Branca Ferreira ◽  
Joao Silva ◽  
Isabel Barbosa ◽  
Susana Roncon ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Follicular Lymphoma ◽  
Haematopoietic Stem Cell Transplantation ◽  
Graft Failure ◽  
Progressive Disease ◽  
Haematopoietic Stem Cell ◽  
Reduced Intensity Conditioning ◽  
Allogeneic Hsct ◽  
Reduced Intensity

Abstract Reduced-intensity conditioning (RIC) regimens is being increasingly used for allogeneic haematopoietic stem cell transplantation (HSCT) in recent years for follicular lymphoma (FL) and chronic lymphocytic leukaemia (CLL). The lower risk of transplant related toxicity associated with RIC regimens makes allogeneic transplantation applicable to patients (pt) with haematological malignancies resistant to conventional therapy and/or in poor medical condition, while preserving the putative graft-versus-tumour effect (GVT). From May 99 to January 07, 31 recipients were studied. Twenty two pt (71%) with FL: 14pt CR2; 4pt PR; 2pt resistant relapse; 1pt graft failure; 1pt advanced disease and 9pt with CLL in PR, underwent to allogeneic HSCT from HLA-matched (31) sibling donors, after treatment with fludarabine 30 mg/m2/d iv × 5 + busulfan 4 mg/Kg/d × 2 ± anti-T lymphocyte globuline (10 mgKg/d) × 4 or fludarabine 30 mg/m2/d iv × 5 + cyclophosphamide (1g/m2/d) × 3 + alentuzumab 20mg/d × 5 (pt with graft failure). Stem cell source was unmanipulated peripheral blood progenitor cells. Median number of CD34+ cells infused: 6,0 × 106/Kg (3,3–12,0). CsA 3 mg/kg/d was given from day-1 until day +90 then tapered progressively, associated with Micophenolate mofetil d0 until d+84. Results: In 31 evaluable pt hematological recovery have a median time to neutrophils ≥0.5×109/L of 13d. (3–37+) and platelets ≥20 × 109/L of 11 d. (9–105+). Transfusion requirements: median: 4 RBC units and 2 platelet transfusions per pt. Median day of discharge: d.15. Hepatic veno-occlusive disease and severe mucositis did not occur. Chimerism analysis (day +28) showed donor engraftment in all pts–mixed in 5 and full in 26 (full in graft failure pt after second transplant). 36±9,2% pts developed clinical grade 2–4 aGvHD and 68,9±10,8% developed cGvHD. Four pt had relapsed/progressive disease. Non relapse mortality occurred in 3 pts with low performance status and chemotherapy resistant disease. At 3,6 years median overall survival (OS) is 85.2±6.9%. Twenty eight pts are alive with a median follow-up of 3.6 years. Progression free survival (PFS) at 3 years is 84,1±7,1 %. Aimed to induce GvT effect, one pt with progressive disease, without GvHD was assigned to receive donor lymphocyte infusions (DLI) at regular intervals achieved stable disease. These results show that RIC regimen are well tolerated, have a low risk of transplant related mortality and are able to ensure a sustained engraftment. RIC is becoming the standard approach in allogeneic HSCT for FL/CLL and the increased risk of late disease progression might be manipulated with GvT effect associated with posterior DLI.

scholarly journals Total Marrow Irradiation for Second Allogeneic Haematopoietic Stem Cell Transplantation in Patients with Advanced Acute Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 32-32
Author(s):  
Alida Dominietto ◽  
Stefano Vagge ◽  
Susanta Hui ◽  
Carmen Di Grazia ◽  
Teresa Lamparelli ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Leukemia ◽  
Haematopoietic Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
Haematopoietic Stem Cell ◽  
High Dose ◽  
Allogeneic Hsct ◽  
Graft Versus Host ◽  
Total Marrow Irradiation ◽  
Alpha Beta

Background. Relapse after allogeneic haematopoietic stem cell transplantation (HSCT) is associated with very poor outcomes. A myeloablative conditioning regimen for patients with advanced acute leukemia before second allogeneic HSCT is crucial to better control the disease, but the risk of transplant mortality due to toxic complications is very high. Total Marrow Irradiation (TMI) is a novel high precision radiation treatment, alternative to standard Total Body Irradiation (TBI) conditioning regimen, allows to deliver therapeutic radiation doses over extensive selected targets while substantially reducing radiation to vital organs to preserve their functions. Aim of the pilot study. To evaluate the efficacy of high dose per fraction TMI in combination with thiotepa, fludarabine and alkeran as conditioning regimen in 9 patients with acute leukemia relapsed after a first allogeneic HSCT. Patients and Methods. Nine patients relapsed after first allogeneic HSCT received a second allogeneic HSCT, 7 from haploidentical, 1 from unrelated (UD) 10/10 and 1 from HLA-identical sibling (SIB) donor. The conditioning regimen consisted of: TMI 8 Gy in 5 patients on day -8 -7 or TMI 12 Gy in 4 patients on day -9 -8 -7, plus Thiotepa 5 mg/Kg on day -6, Fludarabine 50 mg/mq on day -5 -4 -3, alkeran 140 mg/mq on day -2. TMI was delivered in daily single fraction dose of 4 Gy, instead of the conventional 2 Gy in order to potentially enhance the biological effective dose approximately 20% to 60% (for a total dose of 12 Gy), considering alpha/beta ratio between 10-1.49, while total dose of 8 Gy in 2 fractions schedule is potentially equivalent to six fractions of conventional TBI for low alpha/beta ratio. Graft versus host disease (GvHD) prophylaxis for SIB and UD consisted of cyclosporine methotrexate and ATG, whereas for HAPLO it was high dose post-transplant cyclophosphamide (PT-CY), cyclosporine and mycophenolate. The median age was 45 years (range, 19-70 years); 3 patients were in remission, 6 had active disease at the time of the second allogeneic HSCT. The median number of nucleated cells infused was 4.3 x 10e8/Kg (range 2.6-7.7). Four patients received peripheral blood and 5 patients received unmanipulated bone marrow cells. Results. The median time to neutrophil counts of > 0.5 x 10e9/L was 16 days (range 13-22) and to platelet counts of > 20 x 10e9/L was 19 days (range 11-27) respectively. All the patients showed a full donor chimerism on day 30 after transplant; none of the patients had rejection. Three patients developed acute graft versus-host disease (aGvHD) grade I-II and 1 patient had moderate chronic GvHD. During the neutropenic phase of the transplant one patient developed a sepsis from Pseudomonas Aeruginosa; one patient had pericardial effusion and one patient had mucositis grade II. The median follow up was 528 days (range 227-858). Day +30 and day +100 transplant related mortality were 0. Two patients died of transplant related complications; both died of interstitial pneumonia and received TMI 12 Gy. Two patients died of leukemia and they were not in remission at the time of the transplant. The actuarial 17 months disease free-survival (DFS) is 53%. Conclusions. This is the first report demonstrating the safety and the efficacy of the TMI conditioning regimen in patients with advanced acute leukemia receiving second allogeneic transplantation with encouraging outcome in terms of engraftment, early toxocity, GvHD and relapse. Disclosures No relevant conflicts of interest to declare.

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