Peripheral blood progenitor cell collection without close monitoring of peripheral blood CD34+ cells: A feasible strategy for multiple myeloma or pre-treated Non-Hodgkin’s Lymphoma patients mobilized with low-dose cyclophosphamide plus G-CSF

BackgroundDaily monitoring of peripheral blood CD34+ cells may not be necessary for all patients with hematologic malignancies for adequate peripheral blood progenitor cells (PBPC) mobilization and harvesting. We therefore designed a regimen for PBPC mobilization in patients with multiple myeloma or pre-treated Non-Hodgkin’s lymphoma based on a combination of low-dose cyclophosphamide (Cy) plus granulocyte colony-stimulating factor (G-CSF) without daily monitoring of peripheral blood CD34+ cells.Study design and methodsA prospective study was performed on patients with multiple myeloma (n = 22) or pre-treated Non-Hodgkin’s lymphoma (n = 17) whose PBPC were harvested according to the following regimen: 1.5 g/m² Cy at day 1, 12 μg/kg/day G-CSF from day +7 to +11 avoiding daily monitoring of peripheral blood CD34+ cells and two consecutive leukapheresis at days +12 and +13. The optimum threshold of 2 × 10⁶ CD34+ cells per kg was established.ResultsThe proportion of patients with higher CD34+ cell yield after two leukapheresis was similar: multiple myeloma (16/22–72.7%) and Non-Hodgkin’s lymphoma (12/17–70.6%). Exposure to radiotherapy and greater than two prior chemotherapy regimens were significantly associated with lower yield in multiple myeloma (p = 0.002) and Non-Hodgkin’s lymphoma patients (p = 0.002), respectively.ConclusionOur data suggested that adequate yields of CD34+ cells may be achieved in multiple myeloma or pre-treated Non-Hodgkin’s lymphoma mobilized with low-dose Cy plus G-CSF regardless of the daily monitoring of peripheral blood CD34+ cells.     

The clearance time of infused hematopoietic stem cell from the blood circulation

There is no detailed information about the clearance time of infused hematopoietic stem cell (HSC) from the blood circulation in humans. In this prospective study, peripheral blood CD34+ cell counts were detected during the 4 days period following autologous HSC transplantation in 20 patients by means of flow cytometry. The median CD34+ cells were at the highest level in the first hour and decreased below pre-infusion values on the first day after HSC infusion. By nonparametric analysis, positive correlation was found between CD34+ cell levels at the first hour and the post-thaw CD34+ cell dose (r = 0.57, p = 0.01). An inverse correlation was determined between CD34+ cell levels at the first hour and neutrophil engraftment (r = ?0.54, p = 0.01). Compared with the patients having CD34+ cell count of ?2 μL^?1 in the first hour following HSC infusion, the patients having CD34+ cell count of <2 μL^?1 had delayed both neutrophil (20 vs. 12, p = 0.008) and platelet (47 vs. 11, p = 0.01) engraftments. Our results indicated that infused HSCs were removed from the blood circulation within 1 day. In addition, CD34+ cell levels at the first hour may be used as an important indicator to predict the delay of neutrophil and platelet engraftments.     

Quantifying loss of CD34+ cells collected by apheresis after processing for freezing and post-thaw

Introduction: CD34⁺ cells collected for autologous bone marrow transplantation (BMT) are usually quantified in the apheresis product after collection, but the necessity to repeat these measures post-thaw is controversial.Methods: We examined the loss of CD34⁺ cells after collection, preparation for freezing and post-thaw in apheresis products collected for BMT.Results: Median number of CD34⁺ cells collected per unit was 1.61 × 10⁶/kg, viability: 97–100%. This number decreased to 1.38 × 10⁶/kg, viability: 96–100% before freezing and was 1.17 × 10⁶/kg post-thaw. Viability decreased to 86–98%. The relative loss of viable PBHPC showed an inverse correlation with the ratio “CD34⁺ cells/total nucleated cells” (r = ?0.45; p = <0.0005). This relative loss was largest in patients with Hodgkin’s lymphoma.Conclusion: Cryopreservation and thawing of PBHPCs in leukapheresis products provokes a small but significant stem cell loss. So, quantification of viable CD34⁺ cells post-thaw is important, especially in poorly mobilizing patients. Besides, the ratio “CD34⁺ cells/total nucleated cells” after leukapheresis is an important parameter for prediction of neutrophil recovery after BMT.     

The relationship of CD34+ dosage and platelet recovery following high dose chemotherapy and autologous CD34+ reinfusion in multiple myeloma

Autologous hematopoietic stem cell transplantation (ASCT) is an established treatment for multiple myeloma (MM), yet the impact of transplanted CD34+ cell dose remains unresolved, especially in patients over the age of 65 years. Data was collected from 207 consecutive ASCT patients to determine the relationship between CD34+ infusion count and short-term and long-term platelet recovery. For MM patients under the age of 65 years (n = 155), CD34+ dosage correlates with time to platelet engraftment (p < 0.001) and platelet count at 30 days (p = 0.003), but not with long-term platelet counts at 180 or 360 days from the CD34+ reinfusion. For MM patients aged 65 years or older (n = 46), CD34+ dosage did not correlate with time to platelet engraftment, but did correlate with both short-term and long-term platelet counts at 30 (p < 0.001), 180 (p = 0.021), and 360 days (p = 0.005). Exploratory regression analysis was done to explore platelet stability following the current minimum CD34+ dosage reinfusion. For MM patients under the age of 65 years, the minimum standard CD34+ dosage of 2 × 10⁶ cells/kg was sufficient for a timing to platelet engraftment of <21 days and short-term platelets count ≥150 × 10⁹/L at 30 days. Alternatively, for MM patients aged 65 years or older, the CD34+ dosage of 2 × 10⁶ cells/kg was insufficient for platelet counts ≥150 × 10⁹/L at 30 and only marginally attainable at 360 days suggesting that in elderly MM patients a higher CD34+ dosage may be required for platelet recovery and possibly long-term platelet stability.     

Factors associated with peripheral blood stem cell yield in healthy pediatric donors

Background and Objectives

Although several studies have reported on the use of children as donors for peripheral blood stem cells (PBSC), data on the predictive factors of CD34+ stem cell yield in healthy pediatric donors are very limited.

Peripheral blood stem cell collection for allogeneic hematopoietic stem cell transplantation: Practical implications after 200 consequent transplants

Background

Proper stem cell mobilization is one of the most important steps in hematopoietic stem cell transplantation (HSCT). The aim of this paper is to share our 6 years’ experience and provide practical clinical approaches particularly for stem cell mobilization and collection within the series of more than 200 successive allogeneic HSCT at our transplant center.

Use of Laboratory Tests to Guide Initiation of Autologous Hematopoietic Progenitor Cell Collection by Apheresis: Results From the Multicenter Hematopoietic Progenitor Cell Collection by Apheresis Laboratory Trigger Survey

Limited literature describes the value of laboratory “triggers” to guide collection of peripheral blood (PB) hematopoietic progenitor cells (HPCs) by apheresis [HPC(A)]. We used a web-based survey to determine which parameters are used to initiate autologous HPC(A) collection in adult and pediatric patients and to identify common practice patterns. Members of the AABB Cellular Therapy Product Collection and Clinical Practices Subsection and the American Society for Apheresis HPC Donor Subcommittee drafted and developed relevant survey questions. A web link to the survey was distributed by electronic newsletter or email. Responses from 67 programs that perform autologous HPC(A) collections, including academic medical centers (n = 46), blood centers (n = 10), community hospitals (n = 5), and a variety of other medical institutions (n = 6), were analyzed. Ninety-three percent (62/67) of programs used a laboratory parameter to initiate HPC(A) collection. In both adult (40/54, 74%) and pediatric (29/38, 76%) patients, the PB CD34 + cell count was the most common parameter used to initiate HPC(A) collection. The median PB CD34 + trigger value was 10/μL for both patient populations. Among centers routinely using the PB CD34 + cell count to initiate apheresis, 51% (22/43) first sent the test before the patient presented for collection. Although more than 90% of centers used a laboratory test to trigger apheresis in cytokine-mobilized (44/48) or chemomobilized patients (50/53), only 57% (30/53) used a laboratory trigger if the patient was mobilized with granulocyte colony-stimulating factor plus plerixafor. Forty-two percent (21/50) of programs that routinely measured the PB CD34 + count before collection and discontinued further HPC(A) collection based on product CD34 + cell yield also stopped if the PB CD34 + value before apheresis was considered too low to proceed. Most programs use the PB CD34 + cell count to trigger autologous HPC(A) collection. Some centers also use this parameter to stop further collections. Laboratory tests are used less frequently to initiate apheresis when patients are mobilized with plerixafor. These data reveal ongoing diversity in clinical practices and suggest that consensus guidelines on use of laboratory parameters may further optimize HPC(A) collection.     

Automated red blood cell depletion in ABO incompatible grafts in the pediatric setting

Bone marrow ABO incompatible transplantations require graft manipulation prior to infusion to avoid potentially lethal side effects. We analyzed the influence of pre-manipulation factors (temperature at arrival, transit time, time of storage at 4 °C until processing and total time from collection to red blood cell depletion) on the graft quality of 21 red blood cell depletion procedures in ABO incompatible pediatric transplants. Bone marrow collections were processed using the Spectra Optia^® (Terumo BCT) automated device. Temperature at arrival ranged between 4 °C and 6 °C, median transit time was 9.75 h (range 0.33–28), median time of storage at 4°–6 °C until processing was 1.8 h (range 0.41–18.41) and median time from collection to RBC depletion was 21 h (range1–39.4). Median percentage of red blood cell depletion was 97.7 (range 95.4–98.5), median mononuclear cells recovery was 92.2% (range 40–121.2), median CD34+ cell recovery was 93% (range 69.9–161.2), median cell viability was 97.7% (range 94–99.3) and median volume reduction was 83.9% (range 82–92). Graft quality was not significantly different between BM units </> median age. Our preliminary data show that when all good manifacturing practices are respected the post-manipulation graft quality is excellent also for those units processed after 24 h.     

Albumin-based solution is the ideal post-thawing suspension medium for cord blood hematopoietic stem cells: A stability and proliferative evaluation

Background

Cryopreservation and thawing protocols represent key factors for the efficacy of cellular therapy products, such as hematopoietic stem cells (HSCs). While the HSC cryopreservation has already been standardized, the thawing procedures have been poorly studied. This study aimed to evaluate the thawing and washing protocol of cord blood (CB) derived HSCs or the HPC(CB), by selecting the optimal thawing solution and determining CD34+ cells' stability over time.

Study Design and Methods

Seven cryopreserved CB products were thawed, washed, and resuspended in three different solutions (10% Dextran40 in NaCl equally prepared with 5% human albumin; 5% human albumin in PBS/EDTA; and normal saline) and stored at 4°C (±2°C). Mononuclear cell (MNC) count, CD45+/CD34+ cell enumeration, and cell viability were tested at 0, 1, 2, 4, 6, 8, 12, 24, 36, and 48 h. The protocol with the selected solution was further validated on additional 10 CB samples. The above parameters and the colony-forming unit (CFU) assay were analyzed at time points 0, 2, 4, 6, and 8 h.

Results and Discussion

The results showed that the 5% human albumin was the most suitable thawing solution. MNCs were stable up to 4 h (p = 0.009), viable CD45+ cells were unstable even at 2 h (p = 0.013), and viable CD34+ cells were stable until 6 h (p = 0.019). The CFU assay proved the proliferative potential up to 8 h, although significantly decreased after 4 h (p = 0.013), and correlated with the viable CD34+ cell counts. We demonstrated that the post-thawed and washed HPC(CB) using 5% human albumin is stable for up to 4 h.     

Low-dose all-trans retinoic acid enhances cytotoxicity of cisplatin and 5-fluorouracil on CD44+ cancer stem cells

Cis-diamminedichloridoplatinum(II)(CDDP)-based combination chemotherapy is frequently used in gastrointestinal cancer. The synergistic mechanism of all-trans retinoic acid (ATRA), cisplatin (CDDP) and 5-fluorouracil (5-FU) in combination remains unclear. Despite their potent antitumor properties, resistance to CDDP and 5-FU develops frequently in tumors. To clarify this mechanism, we determined the sensitivity to each drug and their combination in two gastrointestinal cancer stem cells (CSCs) subpopulation.Here, we report the identification and separation of CD44⁺ cells from human gastric carcinoma (AGS) and human esophageal squamous cell carcinoma (KYSE-30) cancer cell lines by magnetic activated cell sorting (MACS). We allowed the CD44^± cells to grow 6 days at a subtoxic concentration of ATRA and then treated with different concentration of CDDP and 5-FU for 24 h. The cytotoxicity was examined by cell proliferation MTT assay. Additionally, AO/EB staining was used for detection of apoptotic cells. In order to determine whether the growth inhibition was also associated with changes in cell cycle distribution, cell cycle analysis was performed using flow cytometry.Low concentration of ATRA (1 μM, 6days) followed by 5-FU and CDDP was found to be more effective than either drugs alone, thus resulting in synergistic cytotoxicity in Kyse-30 and AGSCD44^± cells. Furthermore, there was an indication that the combination of ATRA with 5FU and CDDP caused an increase in cell cycle arrest in G2/M and G0/G1.We conclude that low concentration of ATRA enhances the cytotoxicity of CDDP and 5FU by facilitating apoptosis and cell cycle arrest in gastrointestinal CSCs and provide a rational basis for the design of novel, well-tolerated CDDP- and 5FU-based chemotherapy in human gastrointestinal carcinoma.     

Influence of pre-analytical and analytical factors on osteoprotegerin measurements

IntroductionOsteoprotegerin (OPG), an osteoclastogenesis inhibitor implicated in bone remodelling, has emerged as a potential biomarker for cardiovascular disease. In order to implement OPG determination in the clinical laboratory, it is crucial to identify the most appropriate specimen type, preparation and measurement conditions. The present study focuses on identifying the pre-analytical variables that may influence OPG measurements.MethodsSerum and plasma (in EDTA, heparin and citrate) were collected from 45 healthy volunteers (men (n = 21, 46.7%), women (n = 24, 53.3%)). OPG was analysed by ELISA. The influence of the centrifugation speed, the number of freeze–thaw cycles, delay in sample processing, thermo-stability and endogenous interfering agents (haemolysis, triglycerides, bilirubin, cholesterol and RANKL) were studied.ResultsOPG concentrations were significantly lower (p < 0.0001) in serum (1015 ± 357 pg/mL) than in all plasma samples (1314 ± 448 pg/mL in EDTA, 1209 ± 417 pg/mL in heparin and 1260 ± 498 pg/mL in citrate).Increasing centrifugation speed (200 g to 3000 g) did not change serum OPG concentration (p = 0.88). However, OPG concentration significantly increased when centrifuged serum samples were stored at 48 h at room temperature (p < 0.0001). Repeated freeze–thaw cycles did not modify OPG levels until 4 cycles (p < 0.0001). Increasing time before processing the samples (2 h and 6 h) raised OPG concentrations both at room temperature (p < 0.0001) or 4 °C (p < 0.001).Positive concentration-dependent interference of triglycerides was found in the analysed pooled samples; however, OPG concentrations were falsely diminished with haemoglobin interference. Bilirubin, cholesterol and RANKL did not interfere with OPG measurements.     

Two versus three day upfront use of granulocyte-colony stimulating factor in healthy bone marrow donors for pediatric bone marrow transplantation

In order to decrease donors’ exposure to granulocyte-colony stimulating factor (G-CSF), we compared the effect of two versus three days of G-CSF priming on CD34+ yield in bone marrow (BM) harvest. Although the number of BM-CD34+ cells was higher in 3 day G-CSF priming, we achieved the same number of CD34+ cells per recipient’s weight in 2 day G-CSF priming group, too. In addition, the number of total nucleated cells (TNC) harvested from BM were similar with two or three day regimen. But mononuclear cells (MNC) of the BM graft was higher in the 3 day G-CSF priming group. Similar to CD34+ cell numbers, BM harvest yielded similar TNC, and MNC numbers per kilogram of the recipient. We also found that, young donors (≤10 year) had more peripheral blood MNC, bone marrow MNC and CD34+ cell numbers. Another interesting finding of this study was obtaining adequate number of peripheral blood stem cells for leukapheresis with three day G-CSF administration. Since engrafment times were also similar in two groups, we concluded that 2-days G-CSF priming was resulted in sufficient mobilization of BM stem cells.     

Students insert the laryngeal tube quicker and more often successful than the esophageal–tracheal combitube in a manikin

BackgroundEndotracheal intubation remains the standard of airway management. Because intubation skills are difficult to acquire, for medical students teaching of easier to learn techniques should be considered.MethodsWe retrospectively analyzed data that were collected in a University teaching facility. 264 medical students were taught how to use laryngeal tube (LT) and Esophageal Tracheal Combitube^® (ETC) in a manikin. The students underwent one of two different types of extraglottic airway management training consisting of either long lecture (30 min) and intensive training (2 h) (group IT, n = 48), or brief (10 min) lecture and 20 min of training (group BT, n = 216). Both groups underwent a test 6 weeks after training, group IT had an additional test 24 h after training.ResultsAfter 24 h students in group IT were faster using the LT than the ETC (31.7 s ± 2.1 vs. 51.9 s ± 5.8, p < 0.001). Up to 6 weeks after training students were able to place the LT significantly faster than the ETC in both groups (26.5 s ± 2.1 vs. 53.9 s ± 5.8 group IT and 43.4 s ± 1.6 vs. 103.8 s ± 4.4 group BT, p < 0.001). At 24 h and 6 weeks following intensive training, there was no statistical difference in the time required for insertion of either device.ConclusionFollowing different training scenarios in a manikin, students were able to place the LT much faster than the ETC. Even brief training was sufficient to generate short insertion times for the LT.     

Long-term stability of soluble ST2 in frozen plasma samples

ObjectiveThe aim of this study was to investigate the long-term in vitro stability of soluble ST2 (sST2).Design and methodsEDTA plasma samples were drawn from 15 individuals with various diseases. The Presage^TM ST2 assay was used for measurement of sST2 concentrations directly after blood collection and after storing plasma samples for 18 months at ?20 °C and ?80 °C. The default criterion for analyte stability was set at 95%.ResultssST2 concentrations in the 15 individuals ranged from 12 U/mL to 140 U/mL. Directly after blood collection, the mean (± SD) sST2 concentration was 51 ± 37 U/mL, and absolute analyte recoveries were 50 ± 35 U/mL and 51 ± 34 U/mL after storage of samples for 18 months at ?20 °C and ?80 °C, respectively. Relative analyte recoveries after 18 months of storage at ?20 °C and ?80 °C were 99 ± 5% and 101 ± 7%.ConclusionsST2 is stable for at least 1.5 years in plasma samples stored at ?20 °C and ?80 °C.     

Risk factors for poor mobilization in solid tumors: How effectively can we mobilize patients with solid tumors?

Background

In the literature, risk factors for poor mobilization were tried to identify. However, most of the studies consisted heterogeneous group of patients including both hematologic and oncologic malignancies. In this study, we aimed to identify the risk factors for poor mobilization in adults with solid tumors.

Stability of plasma adrenocorticotrophic hormone (ACTH): Influence of hemolysis,rapid chilling,time, and the addition of a maleimide

ObjectivesThe aim of this study was to examine the effects of hemolysis, rapid chilling, time, and the addition of a maleimide on the stability of human plasma ACTH measurements.Design and methodsPartially hemolyzed EDTA blood (n = 10), initially at 37 °C, was centrifuged at 4 °C either immediately or after rapid chilling in ice/water. Plasma ACTH was then measured either immediately, or after 1 h at 22 °C with or without the addition of 2 mM N-phenyl maleimide (NPM).ResultsFor 0.2% hemolysis compared to no hemolysis, the mean (±SEM) loss with immediate centrifugation and immediate ACTH measurement was 11 ± 1%. This loss was significantly (p < 0.002) reduced to 6 ± 1% by an initial rapid chilling of the samples. For analysis after 1 h at 22 °C, the addition of NPM decreased the loss of ACTH from 15 ± 2% to 2 ± 2% (p < 0.002).ConclusionRapid chilling, prompt analysis, and addition of NPM can each reduce the interference of hemolysis in the measurement of plasma ACTH concentrations.     

Evolution,safety and efficacy of targeted temperature management after pediatric cardiac arrest

BackgroundIt is unknown whether targeted temperature management (TTM) improves survival after pediatric out-of-hospital cardiac arrest (OHCA). The aim of this study was to assess the evolution, safety and efficacy of TTM (32–34 °C) compared to standard temperature management (STM) (<38 °C).MethodsRetrospective, single center cohort study. Patients aged >one day up to 16 years, admitted to a UK Paediatric Intensive Care Unit (PICU) after OHCA (January 2004–December 2010). Primary outcome was survival to hospital discharge; efficacy and safety outcomes included: application of TTM, physiological, hematological and biochemical side effects.ResultsSeventy-three patients were included. Thirty-eight patients (52%) received TTM (32–34 °C). Prior to ILCOR guidance adoption in January 2007, TTM was used infrequently (4/25; 16%). Following adoption, TTM (32–34 °C) use increased significantly (34/48; 71% Chi²; p < 0.0001). TTM (32–34 °C) and STM (<38 °C) groups were similar at baseline. TTM (32–34 °C) was associated with bradycardia and hypotension compared to STM (<38 °C). TTM (32–34 °C) reduced episodes of hyperthermia (>38 °C) in the 1st 24 h; however, excessive hypothermia (<32 °C) and hyperthermia (>38 °C) occurred in both groups up to 72 h, and all patients (n = 11) experiencing temperature <32 °C died. The study was underpowered to determine a difference in hospital survival (34% (TTM (32–34 °C)) versus 23% (STM (<38 °C)); p = 0.284). However, the TTM (32–34 °C) group had a significantly longer PICU length of stay.ConclusionsTTM (32–34 °C) was feasible but associated with bradycardia, hypotension, and increased length of stay in PICU. Temperature <32 °C had a universally grave prognosis. Larger studies are required to assess effect on survival.     

Nitric oxide levels in HIV-infected,untreated patients and HIV-infected patients receiving antiretroviral therapy

The role of nitric oxide (NO) in HIV infection is ambiguous; controversy exists around whether the levels of serum NO are increased or decreased in HIV-infected patients. Thus, it is necessary to reassess NO levels in HIV-infected patients. The aim of this study was to investigate the nitrite/nitrate metabolite (NOx) levels in HIV-infected untreated patients and in HIV-infected patients receiving highly active antiretroviral therapy (HAART), compared with HIV-uninfected individuals (control group). The HIV-infected patients enrolled in this study had been receiving HAART for at least 6 months (HIV-treated) or had not received HAART for at least 6 months (HIV-untreated group). New recommendations encourage initiating treatment in HIV-infected adults at a CD4 cell count of 500 cells/mm³ or less. We also investigated whether levels of NOx were associated with immunophenotypic characteristic of HIV-infected patients. Our results showed a statistically significant increase in NOx levels in the HIV-untreated group (164.0 ± 166.6 μmol/L), compared with both the control (98.9 ± 59.4 μmol/L) and HIV-treated group (71.7 ± 53.3 μmol/L). Multiple regression analysis showed that the differences in NOx level were independent of gender, liver enzyme level, lipid measurement, and hematological parameters. In addition, a lower CD4/CD8 ratio was associated with higher NOx levels in HIV-infected patients. The results further revealed that NOx levels were increased in HIV infection, and that derangement of immune system function was associated with increased NO levels. The levels of NOx were found to decline with the use of HAART, which may contribute to cardiovascular disease in HIV-infected patients.     

l-Arginine and polyamine administration protect β-cells against alloxan diabetogenic effect in Sprague–Dawley rats

In the searching for new substances with the capacity to protect β-cells from the toxic effects of alloxan, we evaluated the effect of l-arginine and the polyamines putrescine, spermidine and spermine in a murine experimental model of diabetes. Diabetes was induced by the i.p. injection of either 200 mg/kg (24-h experiments) or 120 mg/kg (12 days experiments) body weight. l-Arginine and polyamines were administered 10 min before or 10 min after alloxan administration, once its half-life had elapsed, respectively.In the 24-h study, serum glucose (199.8 ± 27.6 mg/dl) and triglyceride (54.6 ± 4.9 mg/dl) concentrations showed a protective effect of spermine, as these parameters were not too high (P ≤ 0.05), compared to the alloxan-treated group (415.4 ± 47.8 and 90.2 ± 11.6 mg/dl, respectively), and were closer to glucose (132.3 ± 6.0 mg/dl) and similar to triglycerides (63.8 ± 7.1 mg/dl) of the control group.A similar pattern was observed on the parameters measured when l-arginine and polyamines were administered daily for 12 days, starting 10 min after a single alloxan administration, which provides evidence that l-arginine and polyamines are effective in impeding the increase in serum glucose, triglyceride and cholesterol concentration showed on day 3 by the alloxan-treated group, as well as a higher acinar cell regenerative capacity as determined by immunohistochemical techniques. Spermine turning out to be more effective than l-arginine, putrescine or spermidine in counteracting the marked hyperglycemia and triglyceridemia showed by the alloxan-treated group and similar in effect when evaluating cholesterolemia.These results show a clear protective role of l-arginine and polyamines over the pancreatic β-cell, in addition to the induction of neogenesis from both ductal and acinar cells that leads to the recovery of endocrine pancreatic function in rats with experimental diabetes.